Skip to main content

Vigor, Effort-Related Aspects of Motivation and Anhedonia

  • Chapter
  • First Online:
Anhedonia: Preclinical, Translational, and Clinical Integration

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 58))

Abstract

In this chapter we provide an overview of the pharmacological and circuit mechanisms that determine the willingness to expend effort in pursuit of rewards. A particular focus will be on the role of the mesolimbic dopamine system, as well the contributing roles of limbic and cortical brains areas involved in the evaluation, selection, and invigoration of goal-directed actions. We begin with a review of preclinical studies, which have provided key insights into the brain systems that are necessary and sufficient for effort-based decision-making and have characterized novel compounds that enhance selection of high-effort activities. Next, we summarize translational studies identifying and expanding this circuitry in humans. Finally, we discuss the relevance of this work for understanding common motivational impairments as part of the broader anhedonia symptom domain associated with mental illness, and the identification of new treatment targets within this circuitry to improve motivation and effort-expenditure.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aberman JE, Salamone JD (1999) Nucleus accumbens dopamine depletions make rats more sensitive to high ratio requirements but do not impair primary food reinforcement. Neuroscience 92:545–552

    Article  CAS  PubMed  Google Scholar 

  • Ang Y-S, Lockwood P, Apps MAJ, Muhammed K, Husain M (2017) Distinct subtypes of apathy revealed by the apathy motivation index. PLoS One 12:e0169938

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ariely D, Norton MI (2008) How actions create--not just reveal--preferences. Trends Cogn Sci 12:13–16

    Article  PubMed  Google Scholar 

  • Arulpragasam AR, Cooper JA, Nuutinen MR, Treadway MT (2018) Corticoinsular circuits encode subjective value expectation and violation for effortful goal-directed behavior, Proc Natl Acad Sci: 201800444

    Google Scholar 

  • Association, American Psychiatric (2013) Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub

    Book  Google Scholar 

  • Bahji A, Mesbah-Oskui L (2021) Comparative efficacy and safety of stimulant-type medications for depression: a systematic review and network meta-analysis. J Affect Disord 292:416–423. https://doi.org/10.1016/j.jad.2021.05.119

    Article  CAS  PubMed  Google Scholar 

  • Bailey MR, Chun E, Schipani E, Balsam PD, Simpson EH (2020) Dissociating the effects of dopamine D2 receptors on effort-based versus value-based decision making using a novel behavioral approach. Behav Neurosci 134(2):101–118. https://doi.org/10.1037/bne0000361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baldo BA, Sadeghian K, Basso AM, Kelley AE (2002) Effects of selective dopamine D1 or D2 receptor blockade within nucleus accumbens subregions on ingestive behavior and associated motor activity. Behav Brain Res 137:165–177

    Article  CAS  PubMed  Google Scholar 

  • Barch DM, Treadway MT, Schoen N (2014) Effort, anhedonia, and function in schizophrenia: reduced effort allocation predicts amotivation and functional impairment. J Abnormal Psychol 123:387–397. https://doi.org/10.1037/a0036299

    Article  Google Scholar 

  • Bardgett ME, Depenbrock M, Downs N, Points M, Green L (2009) Dopamine modulates effort-based decision making in rats. Behav Neurosci 123(2):242–251. https://doi.org/10.1037/a0014625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baum WM, Rachlin HC (1969) Choice as time allocation. J Exp Anal Behav 12:861–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bekhbat M, Treadway MT, Felger JC (2022) Inflammation as a pathophysiologic pathway to anhedonia: mechanisms and therapeutic implications. Curr Top Behav Neurosci. https://doi.org/10.1007/7854_2021_294. Online ahead of print

  • Berke JD (2018) What does dopamine mean? Nat Neurosci 1

    Google Scholar 

  • Berridge KC (2007) The debate over dopamine's role in reward: the case for incentive salience. Psychopharmacology 191(3):391–431. https://doi.org/10.1007/s00213-006-0578-x

    Article  CAS  PubMed  Google Scholar 

  • Berridge KC, Robinson TE (2003) Parsing reward. Trends Neurosci 26(9):507–513. https://doi.org/10.1016/S0166-2236(03)00233-9. Erratum in: Trends Neurosci. 2003 Nov;26(11):581

    Article  CAS  PubMed  Google Scholar 

  • Boekhoudt L, Roelofs TJM, de Jong JW, de Leeuw AE, Luijendijk MCM, Wolterink-Donselaar IG, van der Plasse G, Adan RAH (2017) Does activation of midbrain dopamine neurons promote or reduce feeding? Int J Obes 41(7):1131–1140. https://doi.org/10.1038/ijo.2017.74

    Article  CAS  Google Scholar 

  • Boekhoudt L, Wijbrans EC, Man JHK, Luijendijk MCM, de Jong JW, van der Plasse G, Vanderschuren LJMJ, Adan RAH (2018) Enhancing excitability of dopamine neurons promotes motivational behaviour through increased action initiation. Eur Neuropsychopharmacol 28(1):171–184. https://doi.org/10.1016/j.euroneuro.2017.11.005

    Article  CAS  PubMed  Google Scholar 

  • Bonnelle V, Manohar S, Behrens T, Husain M (2015) Individual differences in premotor brain systems underlie behavioral apathy. Cereb Cortex bhv247

    Google Scholar 

  • Borderies N, Bornert P, Gilardeau S, Bouret S (2020) Pharmacological evidence for the implication of noradrenaline in effort. PLoS Biol 18(10):e3000793. https://doi.org/10.1371/journal.pbio.3000793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bryce CA, Floresco SB (2016) Perturbations in effort-related decision-making driven by acute stress and corticotropin-releasing factor. Neuropsychopharmacology 41(8):2147–2159. https://doi.org/10.1038/npp.2016.15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bryden DW, Brockett AT, Blume E, Heatley K, Zhao A, Roesch MR (2019) Single neurons in anterior cingulate cortex signal the need to change action during performance of a stop-change task that induces response competition. Cereb Cortex 29:1020–1031

    Article  PubMed  Google Scholar 

  • Cagniard B, Balsam P, Brunner D, Zhuang X (2006) Mice with chronically elevated dopamine exhibit enhanced motivation, but not learning, for a food reward. Neuropsychopharmacology 31:1362–1370. https://doi.org/10.1038/sj.npp.1300966

    Article  CAS  PubMed  Google Scholar 

  • Cao J, Slack RD, Bakare OM, Burzynski C, Rais R, Slusher BS et al (2016) Novel and high affinity 2-[(diphenylmethyl)sulfinyl]acetamide (modafinil) analogues as atypical dopamine transporter inhibitors. J Med Chem 59:10676–10691. https://doi.org/10.1021/acs.jmedchem.6b01373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carratalá-Ros C, López-Cruz L, SanMiguel N, Ibáñez-Marín P, Martínez-Verdú A, Salamone JD, Correa M (2020) Preference for exercise vs. more sedentary reinforcers: validation of an animal model of tetrabenazine-induced anergia. Front. Behav Neurosci 13:289. https://doi.org/10.3389/fnbeh.2019.00289

    Article  CAS  Google Scholar 

  • Carratalá-Ros C, López-Cruz L, Martínez-Verdú A, Olivares-García R, Salamone JD, Correa M (2021) Impact of fluoxetine on behavioral invigoration of appetitive and aversively motivated responses: interaction with dopamine depletion. Front Behav Neurosci 15:700182. https://doi.org/10.3389/fnbeh.2021.700182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chapman LJ, Chapman JP, Raulin ML (1976) Scales for physical and social anhedonia. J Abnorm Psychol 85:374–382

    Article  CAS  PubMed  Google Scholar 

  • Chen JJ, Ondo WG, Dashtipour K, Swope DM (2012) Tetrabenazine for the treatment of hyperkinetic movement disorders: a review of the literature. Clin Ther 34(7):1487–1504. https://doi.org/10.1016/j.clinthera.2012.06.010

    Article  CAS  PubMed  Google Scholar 

  • Cocker PJ, Hosking JG, Benoit J, Winstanley CA (2012) Sensitivity to cognitive effort mediates psychostimulant effects on a novel rodent cost/benefit decision-making task. Neuropsychopharmacology 37(8):1825–1837. https://doi.org/10.1038/npp.2012.30. Epub 2012 Mar 28. PMID: 22453140; PMCID: PMC3376315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cofer CN (1972) Motivation and emotion. Scott, Foresman, Glenview

    Google Scholar 

  • Cofer CN, Appley MH (1964) Motivation: theory and research. Wiley, New York

    Google Scholar 

  • Collier GH, Jennings W (1969) Work as a determinant of instrumental performance. J Comp Physiol Psychol 68:659–662

    Article  Google Scholar 

  • Collins LE, Sager TN, Sams AG, Pennarola A, Port RG, Shahriari M, Salamone (2012) The novel adenosine A2A antagonist Lu AA47070 reverses the motor and motivational effects produced by dopamine D2 receptor blockade. Pharmacol Biochem Behav 100:498–505

    Article  CAS  PubMed  Google Scholar 

  • Cooper JA, Tucker VL, Papakostas GI (2014) Resolution of sleepiness and fatigue: a comparison of bupropion and selective serotonin reuptake inhibitors in subjects with major depressive disorder achieving remission at doses approved in the European Union. J Psychopharmacol 28:118–124. https://doi.org/10.1177/0269881113514878

    Article  CAS  PubMed  Google Scholar 

  • Cooper JA, Barch DM, Felice Reddy L, Horan WP, Green MF, Michael T (2019) Effortful goal-directed behavior in schizophrenia: computational subtypes and associations with cognition. J Abnormal Psychol Treadway 128:710

    Article  Google Scholar 

  • Correa M, Wisniecki A, Betz A, Dobson DR, O'Neill MF, O'Neill MJ, Salamone JD (2004) The adenosine A2A antagonist KF17837 reverses the locomotor suppression and tremulous jaw movements induced by haloperidol in rats: possible relevance to parkinsonism. Behav Brain Res 148:47–54

    Article  CAS  PubMed  Google Scholar 

  • Correa M, Pardo M, Bayarri P, López-Cruz L, San Miguel N, Valverde O, Ledent C, Salamone JD (2016) Choosing voluntary exercise over sucrose consumption depends upon dopamine transmission: effects of haloperidol in wild type and adenosine A2AKO mice. Psychopharmacology 233(3):393–404. https://doi.org/10.1007/s00213-015-4127-3

    Article  CAS  PubMed  Google Scholar 

  • Correa M, Pardo M, Carratalá-Ros C, Martínez-Verdú A, Salamone JD (2020) Preference for vigorous exercise versus sedentary sucrose drinking: an animal model of anergia induced by dopamine receptor antagonism. Behav Pharmacol 31(6):553–564. https://doi.org/10.1097/FBP.0000000000000556

    Article  CAS  PubMed  Google Scholar 

  • Correll CU, Schooler NR (2020) Negative symptoms in schizophrenia: a review and clinical guide for recognition, assessment, and treatment. Neuropsychiatr Dis Treat 16:519–534. https://doi.org/10.2147/NDT.S225643

    Article  PubMed  PubMed Central  Google Scholar 

  • Cousins MS, Salamone JD (1994) Nucleus accumbens dopamine depletions in rats affect relative response allocation in a novel cost/benefit procedure. Pharmacol Biochem Behav 49:85–91

    Article  CAS  PubMed  Google Scholar 

  • Cousins MS, Sokolowski JD, Salamone JD (1993) Different effects of nucleus accumbens and ventrolateral striatal dopamine depletions on instrumental response selection in the rat. Pharmacol Biochem Behav 46:943–951

    Article  CAS  PubMed  Google Scholar 

  • Crockett MJ, Siegel JZ, Kurth-Nelson Z, Dayan P, Dolan RJ (2017) Moral transgressions corrupt neural representations of value. Nat Neurosci 20:879–885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • da Silva J, Alves FT, Paixão V, Costa RM (2018) Dopamine neuron activity before action initiation gates and invigorates future movements. Nature 554:244–248

    Article  PubMed  CAS  Google Scholar 

  • Dantzer R (2009) Cytokine, sickness behavior, and depression. Immunol Allergy Clin N Am 29:247–264. https://doi.org/10.1016/j.iac.2009.02.002

    Article  Google Scholar 

  • Demyttenaere K, De Fruyt J, Stahl SM (2005) The many faces of fatigue in major depressive disorder. Int J Neuropsychopharmacol 8:93–105. https://doi.org/10.1017/S1461145704004729

    Article  PubMed  Google Scholar 

  • Desai RI, Kopajtic TA, French D, Newman AH, Katz JL (2005a) Relationship between in vivo occupancy at the dopamine transporter and behavioral effects of cocaine, GBR 12909 [1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl) piperazine] and benztropine analogs. J Pharmacol Exp Ther 315:397–404. https://doi.org/10.1124/jpet.105.091231

    Article  CAS  PubMed  Google Scholar 

  • Desai RI, Kopajtic TA, Koffarnus M, Newman AH, Katz JL (2005b) Identification of a dopamine transporter ligand that blocks the stimulant effects of cocaine. J Neurosci 25:1889–1893. https://doi.org/10.1523/JNEUROSCI.4778-04.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dieterich A, Stech K, Srivastava P, Lee J, Sharif A, Samuels BA (2020) Chronic corticosterone shifts effort-related choice behavior in male mice. Psychopharmacology 237(7):2103–2110. https://doi.org/10.1007/s00213-020-05521-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dieterich A, Floeder J, Stech K, Lee J, Srivastava P, Barker DJ, Samuels BA (2021a) Activation of basolateral amygdala to nucleus accumbens projection neurons attenuates chronic corticosterone-induced behavioral deficits in male mice. Front Behav Neurosci 15:643272. https://doi.org/10.3389/fnbeh.2021.643272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dieterich A, Liu T, Samuels BA (2021b) Chronic non-discriminatory social defeat stress reduces effort-related motivated behaviors in male and female mice. Transl Psychiatry 11(1):125. https://doi.org/10.1038/s41398-021-01250-9

    Article  PubMed  PubMed Central  Google Scholar 

  • Drew MR, Simpson EH, Kellendonk C, Herzberg WG, Lipatova O, Fairhurst S, Kandel ER, Malapani C, Balsam PD (2007) Transient overexpression of striatal D2 receptors impairs operant motivation and interval timing. J Neurosci 27(29):7731–7739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duffy E (1941) The conceptual categories of psychology: a suggestion for revision. Psychol Rev 48:177–203

    Article  Google Scholar 

  • Duffy E (1963) Activation and behavior. Wiley, New York

    Google Scholar 

  • Engelhard B, Finkelstein J, Cox J, Fleming W, Jang HJ, Ornelas S, Koay SA, Thiberge SY, Daw ND, Tank DW (2019) Specialized coding of sensory, motor and cognitive variables in VTA dopamine neurons. Nature 570:509–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farrar AM, Pereira M, Velasco F, Hockemeyer J, Muller CE, Salamone JD (2007) Adenosine A(2A) receptor antagonism reverses the effects of (DA) receptor antagonism on instrumental output and effort-related choice in the rat: implications for studies of psychomotor slowing. Psychopharmacology 191:579–586

    Article  CAS  PubMed  Google Scholar 

  • Farrar AM, Segovia KN, Randall PA, Nunes EJ, Collins LE, Stopper CM, Port RG, Hockemeyer J, Müller CE, Correa M, Salamone JD (2010) Nucleus accumbens and effort-related functions: behavioral and neural markers of the interactions between adenosine A2A and (DA) D2 receptors. Neuroscience 166:1056–1067

    Article  CAS  PubMed  Google Scholar 

  • Fava M, Ball S, Nelson JC, Sparks J, Konechnik T, Classi P et al (2014) Clinical relevance of fatigue as a residual symptom in major depressive disorder. Depress Anxiety 31(3):250–257. https://doi.org/10.1002/da.22199

    Article  PubMed  Google Scholar 

  • Felger JC, Treadway MT (2017) Inflammation effects on motivation and motor activity: role of dopamine. Neuropsychopharmacology 42(1):216–241. https://doi.org/10.1038/npp.2016.143

    Article  CAS  PubMed  Google Scholar 

  • Ferré S (1997) Adenosine-dopamine interactions in the ventral striatum. Implications for the treatment of schizophrenia. Psychopharmacology 133:107–120

    Article  PubMed  Google Scholar 

  • Ferré S, Ciruela F, Canals M, Marcellino D, Burgueno J, Casado V, Hillion J, Torvinen M, Fanelli F, Benedetti PP, Goldberg SR, Bouvier M, Fuxe K, Agnati LF, Lluis C, Franco R, Woods A (2004) Adenosine A2A-dopamine D2 receptor-receptor heteromers. Targets for neuro-psychiatric disorders. Park Relat Disord 10:265–271

    Article  Google Scholar 

  • Ferré S, Quiroz C, Woods AS, Cunha R, Popoli P, Ciruela F, Lluis C, Franco R, Azdad K, Schiffmann SN (2008) An update on adenosine A2A-dopamine D2 receptor interactions: implications for the function of G protein-coupled receptors. Curr Pharm Des 14(15):1468–1474. https://doi.org/10.2174/138161208784480108

    Article  PubMed  PubMed Central  Google Scholar 

  • Filla I, Bailey MR, Schipani E, Winiger V, Mezias C, Balsam PD, Simpson EH (2018) Striatal dopamine D2 receptors regulate effort but not value-based decision making and alter the dopaminergic encoding of cost. Neuropsychopharmacology 43(11):2180–2189. https://doi.org/10.1038/s41386-018-0159-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fitzpatrick CM, Runegaard AH, Christiansen SH, Hansen NW, Jørgensen SH, McGirr JC, de Diego AA, Sørensen AT, Perrier JF, Petersen A, Gether U, Woldbye DPD, Andreasen JT (2019) Differential effects of chemogenetic inhibition of dopamine and norepinephrine neurons in the mouse 5-choice serial reaction time task. Prog Neuropsychopharmacol Biol Psychiatry 90:264–276. https://doi.org/10.1016/j.pnpbp.2018.12.004

    Article  CAS  PubMed  Google Scholar 

  • Floresco SB, Ghods-Sharifi S (2007) Amygdala-prefrontal cortical circuitry regulates effort-based decision making. Cereb Cort 17:251–260

    Article  Google Scholar 

  • Floresco SB, Tse MT, Ghods-Sharifi S (2008) Dopaminergic and glutamatergic regulation of effort- and delay-based decision making. Neuropsychopharmacology 33:1966–1979

    Article  CAS  PubMed  Google Scholar 

  • Font L, Mingote S, Farrar AM, Pereira M, Worden L, Stopper C, Port RG, Salamone JD (2008) Intra-accumbens injections of the adenosine A(2A) agonist CGS 21680 affect effort-related choice behavior in rats. Psychopharmacology 199:515–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frank S (2009) Tetrabenazine as anti-chorea therapy in Huntington disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators. BMC Neurol 9:62. https://doi.org/10.1186/1471-2377-9-62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frank S (2010) Tetrabenazine: the first approved drug for the treatment of chorea in US patients with Huntington disease. Neuropsychiatr Dis Treat 6:657–665. https://doi.org/10.2147/NDT.S6430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gard DE, Kring AM, Gard MG, Horan WP, Green MF (2007) Anhedonia in schizophrenia: distinctions between anticipatory and consummatory pleasure. Schizophr Res 93:253–260

    Article  PubMed  PubMed Central  Google Scholar 

  • Gershman SJ (2021) Resource-rational decision making Rahul Bhui, Lucy Lai 2 and Samuel J Gershman 3, 4. Curr Opin Behav Sci 41:15–21

    Google Scholar 

  • Ghanean H, Ceniti AK, Kennedy SH (2018) Fatigue in patients with major depressive disorder: prevalence, burden and pharmacological approaches to management. CNS Drugs 32:65–74. https://doi.org/10.1007/s40263-018-0490-z

    Article  PubMed  Google Scholar 

  • Guay DR (2010) Tetrabenazine, a monoamine-depleting drug used in the treatment of hyperkinectic movement disorders. Am J Geriatr Pharmacother 8(4):331–373. https://doi.org/10.1016/j.amjopharm.2010.08.006

    Article  CAS  PubMed  Google Scholar 

  • Gullion CM, Rush AJ (1998) Toward a generalizable model of symptoms in major depressive disorder. Biol Psychiatry 44:959–972. https://doi.org/10.1016/s0006-3223(98)00235-2

    Article  CAS  PubMed  Google Scholar 

  • Haber SN, Knutson B (2010) The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35:4–26

    Article  PubMed  Google Scholar 

  • Halahakoon DC, Kieslich K, O’Driscoll C, Nair A, Lewis G, Roiser JP (2020) Reward-processing behavior in depressed participants relative to healthy volunteers: a systematic review and meta-analysis. JAMA Psychiat

    Google Scholar 

  • Hallford DJ, Austin DW (2020) Wanting and liking: testing the factor structure of the temporal experience of pleasure scale in major depression and community samples. Assessment 1073191121998767

    Google Scholar 

  • Hamid AA, Pettibone JR, Mabrouk OS, Hetrick VL, Schmidt R, Vander CM, Weele RT, Kennedy BJ, Aragona, and Joshua D Berke. (2016) Mesolimbic dopamine signals the value of work. Nat Neurosci 19:117–126

    Article  CAS  PubMed  Google Scholar 

  • Hamid AA, Frank MJ, Moore CI (2021) Wave-like dopamine dynamics as a mechanism for spatiotemporal credit assignment. Cell 184:2733–49.e16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hart EE, Gerson JO, Zoken Y, Garcia M, Izquierdo A (2017) Anterior cingulate cortex supports effort allocation towards a qualitatively preferred option. Eur J Neurosci 46(1):1682–1688. https://doi.org/10.1111/ejn.13608

    Article  PubMed  PubMed Central  Google Scholar 

  • Hauber W, Sommer S (2009) Prefrontostriatal circuitry regulates effort-related decision making. Cereb Cortex 19(10):2240–2247. https://doi.org/10.1093/cercor/bhn241

    Article  PubMed  Google Scholar 

  • Hayden BY (2019) Why has evolution not selected for perfect self-control? Philos Trans R Soc B 374:20180139

    Article  Google Scholar 

  • Heilbronner SR, Hayden BY (2016) Dorsal anterior cingulate cortex: a bottom-up view. Annu Rev Neurosci 39:149–170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hershenberg R, Satterthwaite TD, Daldal A, Katchmar N, Moore TM, Kable JW, Wolf DH (2016) Diminished effort on a progressive ratio task in both unipolar and bipolar depression. J Affect Disord 196:97–100

    Article  PubMed  PubMed Central  Google Scholar 

  • Hosking JG, Floresco SB, Winstanley CA (2015) Dopamine antagonism decreases willingness to expend physical, but not cognitive, effort: a comparison of two rodent cost/benefit decision-making tasks. Neuropsychopharmacology 40(4):1005–1015. https://doi.org/10.1038/npp.2014.285

    Article  CAS  PubMed  Google Scholar 

  • Hunt LT, Hayden BY (2017) A distributed, hierarchical and recurrent framework for reward-based choice. Nat Rev Neurosci 18:172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hupalo S, Bryce CA, Bangasser DA, Berridge CW, Valentino RJ, Floresco SB (2019) Corticotropin-releasing factor (CRF) circuit modulation of cognition and motivation. Neurosci Biobehav Rev 103:50–59. https://doi.org/10.1016/j.neubiorev.2019.06.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalaba P, Ilić M, Aher NY, Dragačević V, Wieder M, Zehl M, Wackerlig J, Beyl S, Sartori SB, Ebner K, Roller A, Lukic N, Beryozkina T, Gonzalez ERP, Neill P, Khan JA, Bakulev V, Leban JJ, Hering S, Pifl C, Singewald N, Lubec J, Urban E, Sitte HH, Langer T, Lubec G (2020) Structure-activity relationships of novel thiazole-based modafinil analogues acting at monoamine transporters. J Med Chem 63(1):391–417. https://doi.org/10.1021/acs.jmedchem.9b01938

    Article  CAS  PubMed  Google Scholar 

  • Kelley AE, Baldo BA, Pratt WE, Will MJ (2005) Corticostriatal-hypothalamic circuitry and food motivation: integration of energy, action and reward. Physiol Behav 86:773–795

    Article  CAS  PubMed  Google Scholar 

  • Kendler KS (2016) The phenomenology of major depression and the representativeness and nature of DSM criteria. Am J Psychiatr 173:771–780

    Article  PubMed  Google Scholar 

  • Kennerley SW, Walton ME, Behrens TE, Buckley MJ, Rushworth MF (2006) Optimal decision making and the anterior cingulate cortex. Nat Neurosci 9:940–947

    Article  CAS  PubMed  Google Scholar 

  • Kennerley SW, Dahmubed AF, Lara AH, Wallis JD (2009) Neurons in the frontal lobe encode the value of multiple decision variables. J Cogn Neurosci 21:1162–1178

    Article  PubMed  PubMed Central  Google Scholar 

  • Kennerley SW, Behrens TEJ, Wallis JD (2011) Double dissociation of value computations in orbitofrontal and anterior cingulate neurons. Nat Neurosci 14:1581–1589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klein-Flügge MC, Kennerley SW, Friston K, Bestmann S (2016) Neural signatures of value comparison in human cingulate cortex during decisions requiring an effort-reward trade-off. J Neurosci 36:10002–10015

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kohut SJ, Hiranita T, Hong SK, Ebbs AL, Tronci V, Green J, Garces-Ramirez K, Chun LE, Mereu M, Newman AH, Katz JL, Tanda G (2014) Preference for distinct functional conformations of the dopamine transporter alters the relationship between subjective effects of cocaine and stimulation of mesolimbic dopamine. Biol Psychiatry 76(10):802–809. https://doi.org/10.1016/j.biopsych.2014.03.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kolling N, Behrens TEJ, Mars RB, Rushworth MFS (2012) Neural mechanisms of foraging. Science (New York) 336:95–98

    Article  CAS  Google Scholar 

  • Koob GF, Riley SJ, Smith SC, Robbins TW (1978) Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity, and amphetamine anorexia in the rat. J Comp Physiol Psychol 92:917–927

    Article  CAS  PubMed  Google Scholar 

  • Kring AM, Gur RE, Blanchard JJ, Horan WP, Reise SP (2013) The clinical assessment interview for negative symptoms (CAINS): final development and validation. Am J Psychiatr 170(2):165–172

    Article  PubMed  Google Scholar 

  • López-Cruz L, San Miguel N, Carratalá-Ros C, Monferrer L, Salamone JD, Correa M (2018) Dopamine depletion shifts behavior from activity based reinforcers to more sedentary ones and adenosine receptor antagonism reverses that shift: relation to ventral striatum DARPP32 phosphorylation patterns. Neuropharmacology 138:349–359. https://doi.org/10.1016/j.neuropharm.2018.01.034

    Article  CAS  PubMed  Google Scholar 

  • Mai B, Sommer S, Hauber W (2012) Motivational states influence effort-based decision making in rats: the role of dopamine in the nucleus accumbens. Cogn Affect Behav Neurosci 12:74–84. https://doi.org/10.3758/s13415-011-0068-4

    Article  PubMed  Google Scholar 

  • Mas S, Gassó P, Fernández de Bobadilla R, Arnaiz JA, Bernardo M, Lafuente A (2013) Secondary nonmotor negative symptoms in healthy volunteers after single doses of haloperidol and risperidone: a double-blind, crossover, placebo-controlled trial. Hum Psychopharmacol 28(6):586–593. https://doi.org/10.1002/hup.2350

    Article  CAS  PubMed  Google Scholar 

  • Maslow AH (1943) A theory of human motivation. Psychol Rev 50:370

    Article  Google Scholar 

  • McCullough LD, Salamone JD (1992) Involvement of nucleus accumbens dopamine in the motor activity induced by periodic food presentation: a microdialysis and behavioral study. Brain Res 592:29–36

    Article  CAS  PubMed  Google Scholar 

  • McGlinchey JB, Zimmerman M, Young D, Chelminski I (2006) Diagnosing major depressive disorder VIII: are some symptoms better than others? J Nerv Ment Dis 194:785–790

    Article  PubMed  Google Scholar 

  • Medalla M, Barbas H (2009) Synapses with inhibitory neurons differentiate anterior cingulate from dorsolateral prefrontal pathways associated with cognitive control. Neuron 61:609–620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller AH (2009) Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behav Immun 23:149–158. https://doi.org/10.1016/j.bbi.2008.08.006

    Article  CAS  PubMed  Google Scholar 

  • Mingote S, Weber SM, Ishiwari K, Correa M, Salamone JD (2005) Ratio and time requirements on operant schedules: effort-related effects of nucleus accumbens dopamine depletions. Eur J Neurosci 21:1749–1757

    Article  PubMed  Google Scholar 

  • Mingote S, Font L, Farrar AM, Vontell R, Worden LT, Stopper CM, Port RG, Sink KS, Bunce JG, Chrobak JJ, Salamone JD (2008) Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathwway. J Neurosci 28:9037–9046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mitchell AJ, McGlinchey JB, Young D, Chelminski I, Zimmerman M (2009) Accuracy of specific symptoms in the diagnosis of major depressive disorder in psychiatric out-patients: data from the MIDAS project. Psychol Med 39:1107–1116

    Article  CAS  PubMed  Google Scholar 

  • Morelli M, Pinna A (2002) Interaction between dopamine and adenosine A2A receptors as a basis for the treatment of Parkinson's disease. Neurol Sci 22:71–72

    Article  Google Scholar 

  • Mott AM, Nunes EJ, Collins LE, Port RG, Sink KS, Hockemeyer J, Müller CE, Salamone JD (2009) The adenosine A2A antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure. Psychopharmacology 204:103–112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mukherjee D, Lee S, Kazinka R, Satterthwaite TD, Kable JW (2020) Multiple facets of value-based decision making in major depressive disorder. Sci Rep 10:1–12

    Article  CAS  Google Scholar 

  • Münster A, Sommer S, Hauber W (2018) Dopamine D1 receptors in the medial orbitofrontal cortex support effort-related responding in rats. Eur Neuropsychopharmacol 32:136–141. https://doi.org/10.1016/j.euroneuro.2020.01.008

    Article  CAS  Google Scholar 

  • Münster A, Votteler A, Sommer S, Hauber W (2020) Role of the medial orbitofrontal cortex and ventral tegmental area in effort-related responding. Cereb Cortex Commun 1(1):tgaa086. https://doi.org/10.1093/texcom/tgaa086

    Article  PubMed  PubMed Central  Google Scholar 

  • Newman AH, Ku T, Jordan CJ, Bonifazi A, Xi ZX (2021) New drugs, old targets: tweaking the dopamine system to treat psychostimulant use disorders. Annu Rev Pharmacol Toxicol 61:609–628. https://doi.org/10.1146/annurev-pharmtox-030220-124205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nowend KL, Arizzi M, Carlson BB, Salamone JD (2001) D1 or D2 antagonism in nucleus accumbens core or dorsomedial shell suppresses lever pressing for food but leads to compensatory increases in chow consumption. Pharmacol Biochem Behav 69:373–382

    Article  CAS  PubMed  Google Scholar 

  • Nunes EJ, Randall PA, Santerre JL, Given AB, Sager TN, Correa M, Salamone JD (2010) Differential effects of selective adenosine antagonists on the effort-related impairments induced by (DA) D1 and D2 antagonism. Neuroscience 170:268–280

    Article  CAS  PubMed  Google Scholar 

  • Nunes EJ, Randall PA, Hart EE, Freeland C, Yohn SE, Baqi Y, Müller CE, López-Cruz L, Correa M, Salamone JD (2013) Effort-related motivational effects of the VMAT-2 inhibitor tetrabenazine: implications for animal models of the motivational symptoms of depression. J Neurosci 33(49):19120–19130. https://doi.org/10.1523/JNEUROSCI.2730-13.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nunes EJ, Randall PA, Estrada A, Epling B, Hart EE, Lee CA et al (2014) Effort-related motivational effects of the pro-inflammatory cytokine interleukin 1-beta: studies with the concurrent fixed ratio 5/ chow feeding choice task. Psychopharmacology 231(4):727–736. https://doi.org/10.1007/s00213-013-3285-4

    Article  CAS  PubMed  Google Scholar 

  • Olino TM, McMakin DL, Forbes EE (2018) Toward an empirical multidimensional structure of anhedonia, reward sensitivity, and positive emotionality: an exploratory factor analytic study. Assessment 25:679–690

    Article  PubMed  Google Scholar 

  • Pae CU, Lim HK, Han C, Patkar AA, Steffens DC, Masand PS, Lee C (2007) Fatigue as a core symptom in major depressive disorder: overview and the role of bupropion. Expert Rev Neurother 7(10):1251–1263. https://doi.org/10.1586/14737175.7.10.1251

    Article  CAS  PubMed  Google Scholar 

  • Papakostas GI, Nutt DJ, Hallett LA, Tucker VL, Krishen A, Fava M (2006) Resolution of sleepiness and fatigue in major depressive disorder: a comparison of bupropion and the selective serotonin reuptake inhibitors. Biol Psychiatry 60(12):1350–1355. https://doi.org/10.1016/j.biopsych.2006.06.015

    Article  CAS  PubMed  Google Scholar 

  • Pardo M, Lopez-Cruz L, Valverde O, Ledent C, Baqi Y, Müller CE, Salamone JD, Correa M (2012) Adenosine A2A receptor antagonism and genetic deletion attenuate the effects of dopamine D2 antagonism on effort-based decision making in mice. Neuropharmacology 62:2068–2077

    Article  CAS  PubMed  Google Scholar 

  • Pardo M, López-Cruz L, San Miguel N, Salamone JD, Correa M (2015) Selection of sucrose concentration depends on the effort required to obtain it: studies using tetrabenazine, D1, D2, and D3 receptor antagonists. Psychopharmacology 232(13):2377–2391. https://doi.org/10.1007/s00213-015-3872-7

    Article  CAS  PubMed  Google Scholar 

  • Pardo M, Paul NE, Collins-Praino LE, Salamone JD, Correa M (2020) The non-selective adenosine antagonist theophylline reverses the effects of dopamine antagonism on tremor, motor activity and effort-based decision-making. Pharmacol Biochem Behav 198:173035. https://doi.org/10.1016/j.pbb.2020.173035

    Article  CAS  PubMed  Google Scholar 

  • Pooresmaeili A, Wannig A, Dolan RJ (2015) Receipt of reward leads to altered estimation of effort. Proc Natl Acad Sci 112:13407–13410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Presby RE, Rotolo RA, Hurley EM, Ferrigno SM, Murphy CE, McMullen HP, Desai PA, Zorda EM, Kuperwasser FB, Carratala-Ros C, Correa M, Salamone JD (2021) Sex differences in lever pressing and running wheel tasks of effort-based choice behavior in rats: suppression of high effort activity by the serotonin transport inhibitor fluoxetine. Pharmacol Biochem Behav 202:173115. https://doi.org/10.1016/j.pbb.2021.173115

    Article  CAS  PubMed  Google Scholar 

  • Randall PA, Nunes EJ, Janniere SL, Stopper CM, Farrar AM, Sager TN, Baqi Y, Hockemeyer J, Müller CE, Salamone JD (2011) Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists. Psychopharmacology 216:173–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Randall PA, Pardo M, Nunes EJ, López Cruz L, Vemuri VK, Makriyannis A et al (2012) Dopaminergic modulation of effort-related choice behavior as assessed by a progressive ratio chow feeding choice task: pharmacological studies and the role of individual differences. PLoS One 7(10):e47934. https://doi.org/10.1371/journal.pone.0047934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Randall PA, Lee CA, Nunes EJ, Yohn SE, Nowak V, Khan B et al (2014) The VMAT-2 inhibitor tetrabenazine affects effort-related decision making in a progressive ratio/chow feeding choice task: reversal with antidepressant drugs. PLoS One 9(6):e99320. https://doi.org/10.1371/journal.pone.0099320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Randall PA, Lee CA, Podurgiel SJ, Hart E, Yohn SE, Jones M et al (2015) Bupropion increases selection of high effort activity in rats tested on a progressive/ratio chow feeding choice procedure: implications for treatment of effort-related motivational symptoms. Int J Neuropsychopharmacol 18(2):1–11. https://doi.org/10.1093/ijnp/pyu017

    Article  CAS  Google Scholar 

  • Rangel A, Camerer C, Montague PR (2008) A framework for studying the neurobiology of value-based decision making. Nat rev Neurosci 9:545–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rizvi SJ, Quilty LC, Sproule BA, Anna Cyriac R, Bagby M, Kennedy SH (2015) Development and validation of the dimensional anhedonia rating scale (DARS) in a community sample and individuals with major depression. Psychiatry Res 229:109–119

    Article  PubMed  Google Scholar 

  • Robbins TW, Everitt BJ (2007) A role for mesencephalic dopamine in activation: commentary on Berridge (2006). Psychopharmacology 191:433–437

    Article  CAS  PubMed  Google Scholar 

  • Robbins TW, Koob GF (1980) Selective disruption of displacement behaviour by lesions of the mesolimbic dopamine system. Nature 285:409–412

    Article  CAS  PubMed  Google Scholar 

  • Rotolo RA, Dragacevic V, Kalaba P, Urban K, Zehl M, Roller A, Wackerlig J, Langer T, Pistis M, De Luca MA, Caria F, Schwartz R, Presby RE, Yang JH, Samels S, Correa M, Lubec G, Salamone JD (2019) The novel atypical dopamine uptake inhibitor (S)-CE-123 partially reverses the effort-related effects of the dopamine depleting agent tetrabenazine and increases progressive ratio responding. Front Pharm 10:682. https://doi.org/10.3389/fphar.2019.00682

    Article  CAS  Google Scholar 

  • Rotolo RA, Kalaba P, Dragacevic V, Presby RE, Neri J, Robertson E, Yang JH, Correa M, Bakulev V, Volkova NN, Pifl C, Lubec G, Salamone JD (2020) Behavioral and dopamine transporter binding properties of the modafinil analog (S, S)-CE-158: reversal of the motivational effects of tetrabenazine and enhancement of progressive ratio responding. Psychopharmacology 237(11):3459–3470. https://doi.org/10.1007/s00213-020-05625-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rotolo RA, Presby RE, Tracy O, Asar S, Yang JH, Correa M, Murray F, Salamone JD (2021) The novel atypical dopamine transport inhibitor CT-005404 has pro-motivational effects in neurochemical and inflammatory models of effort-based dysfunctions related to psychopathology. Neuropharmacology 183:108325. https://doi.org/10.1016/j.neuropharm.2020.108325

    Article  CAS  PubMed  Google Scholar 

  • Rudebeck PH, Walton ME, Smyth AN, Bannerman DM, Rushworth MF (2006) Separate neural pathways process different decision costs. Nat Neurosci 9:1161–1168

    Article  CAS  PubMed  Google Scholar 

  • Rzepa E, Fisk J, McCabe C (2017) Blunted neural response to anticipation, effort and consummation of reward and aversion in adolescents with depression symptomatology. J Psychopharmacol 31:303–311

    Article  PubMed  Google Scholar 

  • Salamone JD (1986) Different effects of haloperidol and extinction on instrumental behaviours. Psychopharmacology 88:18–23. https://doi.org/10.1007/BF00310507

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD (1988) Dopaminergic involvement in activational aspects of motivation: effects of haloperidol on schedule induced activity, feeding and foraging in rats. Psychobiology 16:196–206

    Article  CAS  Google Scholar 

  • Salamone JD, Correa M (2002) Motivational views of reinforcement: implications for understanding the behavioral functions of nucleus accumbens dopamine. Behav Brain Res 137:3–25. https://doi.org/10.1016/s0166-4328(02)00282-6

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Correa M (2012) The mysterious motivational functions of mesolimbic dopamine. Neuron 76:470–485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salamone JD, Steinpreis RE, McCullough LD, Smith P, Grebel D, Mahan K (1991) Haloperidol and nucleus accumbens dopamine depletion suppress lever pressing for food but increase free food consumption in a novel food choice procedure. Psychopharmacology 104:515–521

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Cousins MS, Bucher S (1994) Anhedonia or anergia? Effects of haloperidol and nucleus accumbens dopamine depletion on instrumental response selection in a T-maze cost/benefit procedure. Behav Brain Res 65:221–229

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Wisniecki A, Carlson BB, Correa M (2001) Nucleus accumbens dopamine depletions make animals highly sensitive to high fixed ratio requirements but do not impair primary food reinforcement. Neuroscience 105:863–870

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Arizzi M, Sandoval MD, Cervone KM, Aberman JE (2002) Dopamine antagonsts alter response allocation but do not suppress appetite for food in rats: contrast between the effects of SKF 83566, raclopride and fenfluramine on a concurrent choice task. Psychopharmacology 160:371–380

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Correa M, Farrar A, Mingote SM (2007) Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology 191:461–482. https://doi.org/10.1007/s00213-006-0668-9

    Article  CAS  PubMed  Google Scholar 

  • Salamone JD, Yohn S, Lopez-Cruz L, San Miguel N, Correa M (2016a) Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology. Brain 139(Pt 5):1325–1347. https://doi.org/10.1093/brain/aww050

    Article  PubMed  PubMed Central  Google Scholar 

  • Salamone JD, Correa M, Yohn S, Lopez-Cruz L, San Miguel N, Alatorre L (2016b) The pharmacology of effort-related choice behavior: dopamine, depression, and individual differences. Behav Process 127:3–17. https://doi.org/10.1016/j.beproc.2016.02.008

    Article  Google Scholar 

  • Salamone JD, Correa M, Yohn SE, Yang J-H, Somerville M, Rotolo RA, Presby RE (2017) Behavioral activation, effort-based choice, and elasticity of demand for motivational stimuli: basic and translational neuroscience approaches. Motiv Sci 3(3):208–229. https://doi.org/10.1037/mot0000070

    Article  Google Scholar 

  • Salamone JD, Correa M, Ferrigno S, Yang J-H, Rotolo RA, Presby RE (2018) The psychopharmacology of effort-related decision making: dopamine, adenosine, and insights into the neurochemistry of motivation. Pharmacol Rev 70:747–762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salamone JD, Ecevitoglu A, Carratala-Ros C, Presby RA, Edelstein G, Fleeher R, Rotolo RA, Meka N, Srinath S, Masthay JC, Correa M (2022) Complexities and paradoxes in understanding the role of dopamine in incentive motivation and instrumental action: exertion of effort vs. Brain Research Bulletin (in press)

    Google Scholar 

  • Santerre JL, Nunes EJ, Randall PA, Baqi Y, Müller CE, Salamone JD (2012) Behavioral studies with the novel adenosine A2A antagonist MSX-4: reversal of the effects of (DA) D2 antagonism. Pharmacol Biochem Behav 102(4):477–487

    Article  CAS  PubMed  Google Scholar 

  • Schmidt L, Lebreton M, Clery-Melin ML, Daunizeau J, Pessiglione M (2012) Neural mechanisms underlying motivation of mental versus physical effort. PLoS Biol 10:e1001266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmitt KC, Reith ME (2011) The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors. PLoS One 6(10):e25790. https://doi.org/10.1371/journal.pone.0025790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmitt KC, Zhen J, Kharkar P, Mishra M, Chen N, Dutta AK, Reith ME (2008) Interaction of cocaine-, benztropine-, and GBR12909-like compounds with wild-type and mutant human dopamine transporters: molecular features that differentially determine antagonist-binding properties. J Neurochem 107(4):928–940. https://doi.org/10.1111/j.1471-4159.2008.05667.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schweimer J, Hauber W (2006) Dopamine D1 receptors in the anterior cingulate cortex regulate effort-based decision making. Learn Mem 13(6):777–782. https://doi.org/10.1101/lm.409306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schweimer J, Saft S, Hauber W (2005) Involvement of catecholamine neurotransmission in the rat anterior cingulate in effort-related decision making. Behav Neurosci 119:1687–1692. https://doi.org/10.1037/0735-7044.119.6.1687

    Article  CAS  PubMed  Google Scholar 

  • Shafiei N, Gray M, Viau V, Floresco SB (2012) Acute stress induces selective alterations in cost/benefit decision-making. Neuropsychopharmacology 37:2194–2209. https://doi.org/10.1038/npp.2012.69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shenhav A, Botvinick MM, Cohen JD (2013) The expected value of control: an integrative theory of anterior cingulate cortex function. Neuron 79:217–240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shenhav A, Straccia MA, Cohen JD, Botvinick MM (2014) Anterior cingulate engagement in a foraging context reflects choice difficulty, not foraging value. Nat Neurosci 17:1249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shenhav A, Musslick S, Lieder F, Kool W, Griffiths TL, Cohen JD, Botvinick MM (2017) Toward a rational and mechanistic account of mental effort. Annu Rev Neurosci 40:99–124

    Article  CAS  PubMed  Google Scholar 

  • Simpson EH, Kellendonk C, Ward RD, Richards V, Lipatova O, Fairhurst S, Kandel ER, Balsam PD (2011) Pharmacologic rescue of motivational deficit in an animal model of the negative symptoms of schizophrenia. Biol Psychiatry 69(10):928–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simpson EH, Waltz JA, Kellendonk C, Balsam PD (2012) Schizophrenia in translation: dissecting motivation in schizophrenia and rodents. Schizophr Bull 38(6):1111–1117

    Article  PubMed  PubMed Central  Google Scholar 

  • Sink KS, Vemuri VK, Olszewska T, Makriyannis A, Salamone JD (2008) Cannabinoid CB1 antagonists and dopamine antagonists produce different effects on a task involving response allocation and effort-related choice in food-seeking behavior. Psychopharmacology 196:565–574

    Article  CAS  PubMed  Google Scholar 

  • Snaith RP, Hamilton M, Morley S, Humayan A, Hargreaves D, Trigwell P (1995) A scale for the assessment of hedonic tone the Snaith-Hamilton pleasure scale. Br J Psychiatry 167:99–103

    Article  CAS  PubMed  Google Scholar 

  • Soder HE, Cooper JA, Lopez-Gamundi P, Hoots JK, Nunez C, Lawlor VM, Lane SD, Treadway MT, Wardle MC (2021) Dose-response effects of d-amphetamine on effort-based decision-making and reinforcement learning. Neuropsychopharmacology 46:1078–1085

    Article  CAS  PubMed  Google Scholar 

  • Sommer S, Danysz W, Russ H, Valastro B, Flik G, Hauber W (2014) The dopamine reuptake inhibitor MRZ-9547 increases progressive ratio responding in rats. Int J Neuropsychopharmacol 17:2045–2056. https://doi.org/10.1017/S1461145714000996

    Article  CAS  PubMed  Google Scholar 

  • Stotz G, Woggon B, Angst J (1999) Psychostimulants in the therapy of treatment-resistant depression review of the literature and findings from a retrospective study in 65 depressed patients. Dialogues Clin Neurosci 1(3):165–174. PMID: 22034135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki S, Lawlor VM, Cooper JA, Arulpragasam AR, Treadway MT (2021) Distinct regions of the striatum underlying effort, movement initiation and effort discounting. Nat Hum Behav 5:378–388

    Article  PubMed  Google Scholar 

  • Svenningsson P, Le Moine C, Fisone G, Fredholm BB (1999) Distribution, biochemistry and function of striatal adenosine A2A receptors. Prog Neurobiol 59:355–396

    Article  CAS  PubMed  Google Scholar 

  • Tanda G, Li SM, Mereu M, Thomas AM, Ebbs AL, Chun LE, Tronci V, Green JL, Zou MF, Kopajtic TA, Newman AH, Katz JL (2013a) Relations between stimulation of mesolimbic dopamine and place conditioning in rats produced by cocaine or drugs that are tolerant to dopamine transporter conformational change. Pharmacology (Berl) 229(2):307–321. https://doi.org/10.1007/s00213-013-3109-6

    Article  CAS  PubMed Central  Google Scholar 

  • Tanda G, Li SM, Mereu M, Thomas AM, Ebbs AL, Chun LE, Tronci V, Green JL, Zou MF, Kopajtic TA, Newman AH, Katz JL (2013b) Relations between stimulation of mesolimbic dopamine and place conditioning in rats produced by cocaine or drugs that are tolerant to dopamine transporter conformational change. Psychopharmacology 229(2):307–321. https://doi.org/10.1007/s00213-013-3109-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Treadway MT, Buckholtz JW, Schwartzman AN, Lambert WE, Zald DH (2009) Worth the ‘EEfRT’? The effort expenditure for rewards task as an objective measure of motivation and anhedonia. PLoS One 4:e6598

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Treadway MT, Bossaller NA, Shelton RC, Zald DH (2012) Effort-based decision-making in major depressive disorder: a translational model of motivational anhedonia. J Abnorm Psychol 121(3):553–558. https://doi.org/10.1037/a0028813

    Article  PubMed  PubMed Central  Google Scholar 

  • Trifilieff P, Feng B, Urizar E, Winiger V, Ward RD, Taylor KM, Martinez D, Moore H, Balsam PD, Simpson EH, Javitch JA (2013) Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation. Mol Psychiatry 18:1025–1033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vancraeyenest P, Arsenault JT, Li X, Zhu Q, Kobayashi K, Isa K, Isa T, Vanduffel W (2020) Selective mesoaccumbal pathway inactivation affects motivation but not reinforcement-based learning in macaques. Neuron 108(3):568–581.e6. https://doi.org/10.1016/j.neuron.2020.07.013

    Article  CAS  PubMed  Google Scholar 

  • Varazzani C, San-Galli A, Gilardeau S, Bouret S (2015) Noradrenaline and dopamine neurons in the reward/effort trade-off: a direct electrophysiological comparison in behaving monkeys. J Neurosci 35(20):7866–7877. https://doi.org/10.1523/JNEUROSCI.0454-15.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vincent JL, Kahn I, Snyder AZ, Raichle ME, Buckner RL (2008) Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. J Neurophysiol 100:3328–3342

    Article  PubMed  PubMed Central  Google Scholar 

  • Wallace M, Singer G, Finlay J, Gibson S (1983) The effect of 6-OHDA lesions of the nucleus accumbens septum on schedule-induced drinking, wheelrunning and corticosterone levels in the rat. Pharmacol Biochem Behav 18:129–136

    Article  CAS  PubMed  Google Scholar 

  • Walton ME, Bannerman DM, Rushworth MF (2002) The role of rat medial frontal cortex in effort-based decision making. J Neurosci 22:10996–11003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walton ME, Bannerman DM, Alterescu K, Rushworth MF (2003) Functional specialization within medial frontal cortex of the anterior cingulate for evaluating effort-related decisions. J Neurosci 23:6475–6479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walton ME, Groves J, Jennings KA, Croxson PL, Sharp T, Rushworth MF, Bannerman DM (2009) Comparing the role of the anterior cingulate cortex and 6-hydroxydopamine nucleus accumbens lesions on operant effort-based decision making. Eur J Neurosci 29:1678–1691

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang S, Leri F, Rizvi SJ (2022) Clinical and preclinical assessments of anhedonia in psychiatric disorders. Curr Top Behav Neurosci (this volume)

    Google Scholar 

  • Ward RD, Simpson EH, Richards VL, Deo G, Taylor K, Glendinning JI, Kandel ER, Balsam PD (2012) Dissociation of hedonic reaction to reward and incentive motivation in an animal model of the negative symptoms of schizophrenia. Neuropsychopharmacology 37(7):1699–1707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wardle MC, Treadway MT, Mayo LM, Zald DH, de Wit H (2011) Amping up effort: effects of d-amphetamine on human effort-based decision-making. J Neurosci 31:16597–16602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watson R, Harvey K, McCabe C, Reynolds S (2020) Understanding anhedonia: a qualitative study exploring loss of interest and pleasure in adolescent depression. Eur Child Adolesc Psychiatry 29:489–499

    Article  PubMed  Google Scholar 

  • Westbrook A, Ruben van den Bosch JI, Määttä LH, Papadopetraki D, Cools R, Frank MJ (2020) Dopamine promotes cognitive effort by biasing the benefits versus costs of cognitive work. Science 367:1362–1366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winstanley CA, Floresco SB (2016) Deciphering decision making: variation in animal models of effort- and uncertainty-based choice reveals distinct neural circuitries underlying core cognitive processes. J Neurosci 36(48):12069–12079. https://doi.org/10.1523/JNEUROSCI.1713-16.2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Worden LT, Shahriari M, Farrar AM, Sink KS, Hockemeyer J, Müller C, Salamone JD (2009) The adenosine A2A antagonist MSX-3 reverses the effort-related effects of dopamine blockade: differential interaction with D1 and D2 family antagonists. Psychopharmacology 203:489–499

    Article  CAS  PubMed  Google Scholar 

  • Yang JH, Presby RE, Jarvie AA, Rotolo RA, Fitch RH, Correa M, Salamone JD (2020a) Pharmacological studies of effort-related decision making using mouse touchscreen procedures: effects of dopamine antagonism do not resemble reinforcer devaluation by removal of food restriction. Psychopharmacology 237:33–43. https://doi.org/10.1007/s00213-019-05343-8

    Article  CAS  PubMed  Google Scholar 

  • Yang JH, Presby RE, Rotolo RA, Quiles T, Okifo K, Zorda E, Fitch RH, Correa M, Salamone JD (2020b) The dopamine depleting agent tetrabenazine alters effort-related decision making as assessed by mouse touchscreen procedures. Psychopharmacology 237(9):2845–2854. https://doi.org/10.1007/s00213-020-05578-w

    Article  CAS  PubMed  Google Scholar 

  • Yohn SE, Thompson C, Randall PA, Lee CA, Müller CE, Baqi Y et al (2015a) The VMAT-2 inhibitor tetrabenazine alters effort-related decision making as measured by the T-maze barrier choice task: reversal with the adenosine A2A antagonist MSX-3 and the catecholamine uptake blocker bupropion. Psychopharmacology 232(7):1313–1323. https://doi.org/10.1007/s00213-014-3766-0

    Article  CAS  PubMed  Google Scholar 

  • Yohn SE, Santerre JL, Nunes EJ, Kozak R, Podurgiel SJ, Correa M, Salamone JD (2015b) The role of dopamine D1 receptor transmission in effort-related choice behavior: effects of D1 agonists. Pharmacol Biochem Behav 135:217–226. https://doi.org/10.1016/j.pbb.2015.05.003

    Article  CAS  PubMed  Google Scholar 

  • Yohn SE, Collins SL, Contreras-Mora HM, Errante EL, Rowland MA, Correa M, Salamone JD (2016a) Not all antidepressants are created equal: differential effects of monoamine uptake inhibitors on effort-related choice behavior. Neuropsychopharmacology 41(3):686–694. https://doi.org/10.1038/npp.2015.188

    Article  CAS  PubMed  Google Scholar 

  • Yohn SE, Lopez-Cruz L, Hutson PH, Correa M, Salamone JD (2016b) Effects of lisdexamfetamine and s-citalopram, alone and in combination, on effort-related choice behavior in the rat. Psychopharmacology 233(6):949–960. https://doi.org/10.1007/s00213-015-4176-7

    Article  CAS  PubMed  Google Scholar 

  • Yohn SE, Gogoj A, Haque A, Lopez-Cruz L, Haley A, Huxley P et al (2016c) Evaluation of the effort-related motivational effects of the novel dopamine uptake inhibitor PRX-14040. Pharmacol Biochem Behav 148:84–91. https://doi.org/10.1016/j.pbb.2016.06.004

    Article  CAS  PubMed  Google Scholar 

  • Yohn SE, Errante EL, Rosenbloom-Snow A, Sommerville M, Rowland MA, Tokarski K et al (2016d) Blockade of uptake for dopamine, but not norepinephrine or 5-HT, increases selection of high effort instrumental activity: implications for treatment of effort-related motivational symptoms in psychopathology. Neuropharmacology 109:270–280. https://doi.org/10.1016/j.neuropharm.2016.06.018

    Article  CAS  PubMed  Google Scholar 

  • Yohn SE, Arif Y, Haley A, Tripodi G, Baqi Y, Müller CE, Miguel NS, Correa M, Salamone JD (2016e) Effort-related motivational effects of the pro-inflammatory cytokine interleukin-6: pharmacological and neurochemical characterization. Psychopharmacology 233(19–20):3575–3586. https://doi.org/10.1007/s00213-016-4392-9

    Article  CAS  PubMed  Google Scholar 

  • Zaki J, Schirmer J, Mitchell JP (2011) Social influence modulates the neural computation of value. Psychol Sci 22:894–900

    Article  PubMed  Google Scholar 

  • Zénon A, Devesse S, Olivier E (2016) Dopamine manipulation affects response vigor independently of opportunity cost. J Neurosci 36:9516–9525

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael T. Treadway .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Treadway, M.T., Salamone, J.D. (2022). Vigor, Effort-Related Aspects of Motivation and Anhedonia. In: Pizzagalli, D.A. (eds) Anhedonia: Preclinical, Translational, and Clinical Integration. Current Topics in Behavioral Neurosciences, vol 58. Springer, Cham. https://doi.org/10.1007/7854_2022_355

Download citation

Publish with us

Policies and ethics