Abstract
Rationale
Neuropsychological testing is widespread in adult cocaine abusers, but lacking in teens. Animal models may provide insight into age-related neuropsychological consequences of cocaine exposure.
Objectives
The objective of the present study is to determine whether developmental plasticity protects or hinders behavioral flexibility after cocaine exposure in adolescent vs. adult rats.
Methods
Using a yoked-triad design, one rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling cocaine delivery (1.0 mg/kg) self-administered for 18 sessions (starting P37 or P77), followed by 18 drug-free days. Rats next were tested in a strategy set shifting task, lasting 11–13 sessions.
Results
Cocaine self-administration did not differ between age groups. During initial set formation, adolescent-onset groups required more trials to reach criterion and made more errors than adult-onset groups. During the set shift phase, rats with adult-onset cocaine self-administration experience had higher proportions of correct trials and fewer perseverative + regressive errors than age-matched yoked-controls or rats with adolescent-onset cocaine self-administration experience. During reversal learning, rats with adult-onset cocaine experience (self-administered or passive) required fewer trials to reach criterion, and the self-administering rats made fewer perseverative + regressive errors than yoked-saline rats. Rats receiving adolescent-onset yoked-cocaine had more trial omissions and longer lever press reaction times than age-matched rats self-administering cocaine or receiving yoked-saline.
Conclusions
Prior cocaine self-administration may impair memory to reduce proactive interference during set shifting and reversal learning in adult-onset but not adolescent-onset rats (developmental plasticity protective). Passive cocaine may disrupt aspects of executive function in adolescent-onset but not adult-onset rats (developmental plasticity hinders).
Similar content being viewed by others
References
Aine CJ, Woodruff CC, Knoefel JE, Adair JC, Hudson D, Qualls C, Bockholt J, Best E, Kovacevic S, Cobb W, Padilla D, Hart B, Stephen JM (2006) Aging: compensation or maturation? Neuroimage 32:1891–1904
Allen RM, Uban KA, Atwood EM, Albeck DS, Yamamoto DJ (2007) Continuous intracerebroventricular infusion of the competitive NMDA receptor antagonist, LY235959, facilitates escalation of cocaine self-administration and increases break point for cocaine in Sprague-Dawley rats. Pharmacol Biochem Behav 88:82–88
Andersen SL, Thompson AT, Rutstein M, Hostetter JC, Teicher MH (2000) Dopamine receptor pruning in prefrontal cortex during the periadolescent period in rats. Synapse 37:167–169
Bechara A, Dolan S, Denburg N, Hindes A, Anderson SW, Nathan PE (2001) Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers. Neuropsychologia 39:376–389
Bilder RM, Volavka J, Lachman HM, Grace AA (2004) The catechol-O-methyltransferase polymorphism: relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology 29:1943–1961
Birrell JM, Brown VJ (2000) Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci 20:4320–4324
Black YD, Maclaren FR, Naydenov AV, Carlezon WA Jr, Baxter MG, Konradi C (2006) Altered attention and prefrontal cortex gene expression in rats after binge-like exposure to cocaine during adolescence. J Neurosci 26:9656–9665
Bolla KI, Eldreth DA, London ED, Kiehl KA, Mouratidis M, Contoreggi C, Matochik JA, Kurian V, Cadet JL, Kimes AS, Funderburk FR, Ernst M (2003) Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task. Neuroimage 19:1085–1094
Bolla K, Ernst M, Kiehl K, Mouratidis M, Eldreth D, Contoreggi C, Matochik J, Kurian V, Cadet J, Kimes A, Funderburk F, London E (2004) Prefrontal cortical dysfunction in abstinent cocaine abusers. J Neuropsychiatry Clin Neurosci 16:456–464
Booze RM, Lehner AF, Wallace DR, Welch MA, Mactutus CF (1997) Dose-response cocaine pharmacokinetics and metabolite profile following intravenous administration and arterial sampling in unanesthetized, freely moving male rats. Neurotoxicol Teratol 19:7–15
Boulougouris V, Dalley JW, Robbins TW (2007) Effects of orbitofrontal, infralimbic and prelimbic cortical lesions on serial spatial reversal learning in the rat. Behav Brain Res 179:219–228
Cain RE, Wasserman MC, Waterhouse BD, McGaughy JA (2011) Atomoxetine facilitates attentional set shifting in adolescent rats. Dev Cogn Neurosci 1:552–559
Calipari ES, Beveridge TJ, Jones SR, Porrino LJ (2013) Withdrawal from extended-access cocaine self-administration results in dysregulated functional activity and altered locomotor activity in rats. Eur J Neurosci 38:3749–57
Carroll ME, Gao Y, Brimijoin S, Anker JJ (2010) Effects of cocaine hydrolase on cocaine self-administration under a PR schedule and during extended access (escalation) in rats. Psychopharmacology (Berl) 213:817–829
Casey BJ, Davidson MC, Hara Y, Thomas KM, Martinez A, Galvan A, Halperin JM, Rodriguez-Aranda CE, Tottenham N (2004) Early development of subcortical regions involved in non-cued attention switching. Dev Sci 7:534–542
Chase EA, Tait DS, Brown VJ (2012) Lesions of the orbital prefrontal cortex impair the formation of attentional set in rats. Eur J Neurosci 36:2368–2375
Chess AC, Raymond BE, Gardner-Morse IG, Stefani MR, Green JT (2011) Set shifting in a rodent model of attention-deficit/hyperactivity disorder. Behav Neurosci 125:372–382
Colas-Zelin D, Light KR, Kolata S, Wass C, Denman-Brice A, Rios C, Szalk K, Matzel LD (2012) The imposition of, but not the propensity for, social subordination impairs exploratory behaviors and general cognitive abilities. Behav Brain Res 232:294–305
Conrad KL, Ford K, Marinelli M, Wolf ME (2010) Dopamine receptor expression and distribution dynamically change in the rat nucleus accumbens after withdrawal from cocaine self-administration. Neuroscience 169:182–194
Crofts HS, Dalley JW, Collins P, Van Denderen JC, Everitt BJ, Robbins TW, Roberts AC (2001) Differential effects of 6-OHDA lesions of the frontal cortex and caudate nucleus on the ability to acquire an attentional set. Cereb Cortex 11:1015–1026
Czoty PW, Nader MA (2013) Effects of dopamine D2/D3 receptor ligands on food-cocaine choice in socially housed male cynomolgus monkeys. J Pharmacol Exp Ther 344:329–338
Dalton GL, Ma LM, Phillips AG, Floresco SB (2011) Blockade of NMDA GluN2B receptors selectively impairs behavioral flexibility but not initial discrimination learning. Psychopharmacology (Berl) 216:525–535
Deaner RO, Khera AV, Platt ML (2005) Monkeys pay per view: adaptive valuation of social images by rhesus macaques. Curr Biol 15:543–548
Di Pietro NC, Black YD, Green-Jordan K, Eichenbaum HB, Kantak KM (2004) Complementary tasks to measure working memory in distinct prefrontal cortex subregions in rats. Behav Neurosci 118:1042–1051
Drechsler R, Rizzo P, Steinhausen HC (2010) The impact of instruction and response cost on the modulation of response-style in children with ADHD. Behav Brain Funct 6:31
Ersche KD, Roiser JP, Robbins TW, Sahakian BJ (2008) Chronic cocaine but not chronic amphetamine use is associated with perseverative responding in humans. Psychopharmacology (Berl) 197:421–431
Ersche KD, Roiser JP, Abbott S, Craig KJ, Muller U, Suckling J, Ooi C, Shabbir SS, Clark L, Sahakian BJ, Fineberg NA, Merlo-Pich EV, Robbins TW, Bullmore ET (2011) Response perseveration in stimulant dependence is associated with striatal dysfunction and can be ameliorated by a D(2/3) receptor agonist. Biol Psychiatry 70:754–762
Ferrario CR, Gorny G, Crombag HS, Li Y, Kolb B, Robinson TE (2005) Neural and behavioral plasticity associated with the transition from controlled to escalated cocaine use. Biol Psychiatry 58:751–759
Floresco SB (2013) Prefrontal dopamine and behavioral flexibility: shifting from an “inverted-U” toward a family of functions. Front Neurosci 7:62
Floresco SB, Block AE, Tse MT (2008) Inactivation of the medial prefrontal cortex of the rat impairs strategy set-shifting, but not reversal learning, using a novel, automated procedure. Behav Brain Res 190:85–96
Floresco SB, Zhang Y, Enomoto T (2009) Neural circuits subserving behavioral flexibility and their relevance to schizophrenia. Behav Brain Res 204:396–409
Fox HC, Jackson ED, Sinha R (2009) Elevated cortisol and learning and memory deficits in cocaine dependent individuals: relationship to relapse outcomes. Psychoneuroendocrinology 34:1198–1207
Franklin TR, Acton PD, Maldjian JA, Gray JD, Croft JR, Dackis CA, O’Brien CP, Childress AR (2002) Decreased gray matter concentration in the insular, orbitofrontal, cingulate, and temporal cortices of cocaine patients. Biol Psychiatry 51:134–142
Gabriele A, Pacchioni AM, See RE (2012) Dopamine and glutamate release in the dorsolateral caudate putamen following withdrawal from cocaine self-administration in rats. Pharmacol Biochem Behav 103:373–379
Ghods-Sharifi S, Haluk DM, Floresco SB (2008) Differential effects of inactivation of the orbitofrontal cortex on strategy set-shifting and reversal learning. Neurobiol Learn Mem 89:567–573
Gillen RW, Kranzler HR, Bauer LO, Burleson JA, Samarel D, Morrison DJ (1998) Neuropsychologic findings in cocaine-dependent outpatients. Prog Neuropsychopharmacol Biol Psychiatry 22:1061–1076
Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, Nugent TF 3rd, Herman DH, Clasen LS, Toga AW, Rapoport JL, Thompson PM (2004) Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A 101:8174–8179
Haluk DM, Floresco SB (2009) Ventral striatal dopamine modulation of different forms of behavioral flexibility. Neuropsychopharmacology 34:2041–2052
Hankosky ER, Kofsky NM, Gulley JM (2013) Age of exposure-dependent effects of amphetamine on behavioral flexibility. Behav Brain Res 252:117–125
Hanlon CA, Dufault DL, Wesley MJ, Porrino LJ (2011) Elevated gray and white matter densities in cocaine abstainers compared to current users. Psychopharmacology (Berl) 218:681–692
Harvey RC, Dembro KA, Rajagopalan K, Mutebi MM, Kantak KM (2009) Effects of self-administered cocaine in adolescent and adult male rats on orbitofrontal cortex-related neurocognitive functioning. Psychopharmacology (Berl) 206:61–71
Harvey RC, Jordan CJ, Tassin DH, Moody KR, Dwoskin LP, Kantak KM (2013) Performance on a strategy set shifting task during adolescence in a genetic model of attention deficit/hyperactivity disorder: methylphenidate vs. atomoxetine treatments. Behav Brain Res 244:38–47
Hervey AS, Epstein JN, Curry JF, Tonev S, Eugene Arnold L, Keith Conners C, Hinshaw SP, Swanson JM, Hechtman L (2006) Reaction time distribution analysis of neuropsychological performance in an ADHD sample. Child Neuropsychol 12:125–140
Hester R, Garavan H (2004) Executive dysfunction in cocaine addiction: evidence for discordant frontal, cingulate, and cerebellar activity. J Neurosci 24:11017–11022
Jovanovski D, Erb S, Zakzanis KK (2005) Neurocognitive deficits in cocaine users: a quantitative review of the evidence. J Clin Exp Neuropsychol 27:189–204
Kantak KM, Green-Jordan K, Valencia E, Kremin T, Eichenbaum HB (2001) Cognitive task performance after lidocaine-induced inactivation of different sites within the basolateral amygdala and dorsal striatum. Behav Neurosci 115:589–601
Kasperski SJ, Vincent KB, Caldeira KM, Garnier-Dykstra LM, O’Grady KE, Arria AM (2011) College students’ use of cocaine: results from a longitudinal study. Addict Behav 36:408–411
Kerstetter KA, Kantak KM (2007) Differential effects of self-administered cocaine in adolescent and adult rats on stimulus-reward learning. Psychopharmacology (Berl) 194:403–411
Knackstedt LA, Kalivas PW (2007) Extended access to cocaine self-administration enhances drug-primed reinstatement but not behavioral sensitization. J Pharmacol Exp Ther 322:1103–1109
Kolb B, Pellis S, Robinson TE (2004) Plasticity and functions of the orbital frontal cortex. Brain Cogn 55:104–115
Liu Y, Roberts DC, Morgan D (2005) Effects of extended-access self-administration and deprivation on breakpoints maintained by cocaine in rats. Psychopharmacology (Berl) 179:644–651
Madoz-Gurpide A, Blasco-Fontecilla H, Baca-Garcia E, Ochoa-Mangado E (2011) Executive dysfunction in chronic cocaine users: an exploratory study. Drug Alcohol Depend 117:55–58
Marsh AA, Blair KS, Jones MM, Soliman N, Blair RJ (2009) Dominance and submission: the ventrolateral prefrontal cortex and responses to status cues. J Cogn Neurosci 21:713–724
Matochik JA, London ED, Eldreth DA, Cadet JL, Bolla KI (2003) Frontal cortical tissue composition in abstinent cocaine abusers: a magnetic resonance imaging study. Neuroimage 19:1095–1102
Moreno-Lopez L, Stamatakis EA, Fernandez-Serrano MJ, Gomez-Rio M, Rodriguez-Fernandez A, Perez-Garcia M, Verdejo-Garcia A (2012) Neural correlates of the severity of cocaine, heroin, alcohol, MDMA and cannabis use in polysubstance abusers: a resting-PET brain metabolism study. PLoS ONE 7:e39830
Nesher E, Gross M, Lisson S, Tikhonov T, Yadid G, Pinhasov A (2013) Differential responses to distinct psychotropic agents of selectively bred dominant and submissive animals. Behav Brain Res 236: 225–35
Newman LA, McGaughy J (2011) Adolescent rats show cognitive rigidity in a test of attentional set shifting. Dev Psychobiol 53:391–401
O’Malley S, Adamse M, Heaton RK, Gawin FH (1992) Neuropsychological impairment in chronic cocaine abusers. Am J Drug Alcohol Abuse 18:131–144
Paly D, Jatlow P, Van Dyke C, Jeri FR, Byck R (1982) Plasma cocaine concentrations during cocaine paste smoking. Life Sci 30:731–738
Ragozzino ME, Detrick S, Kesner RP (1999) Involvement of the prelimbic-infralimbic areas of the rodent prefrontal cortex in behavioral flexibility for place and response learning. J Neurosci 19:4585–4594
Reeve WV, Schandler SL (2001) Frontal lobe functioning in adolescents with attention deficit hyperactivity disorder. Adolescence 36:749–765
Rossi AF, Pessoa L, Desimone R, Ungerleider LG (2009) The prefrontal cortex and the executive control of attention. Exp Brain Res 192:489–497
Seidman LJ, Biederman J, Faraone SV, Weber W, Mennin D, Jones J (1997) A pilot study of neuropsychological function in girls with ADHD. J Am Acad Child Adolesc Psychiatry 36:366–373
Sowell ER, Thompson PM, Tessner KD, Toga AW (2001) Mapping continued brain growth and gray matter density reduction in dorsal frontal cortex: inverse relationships during postadolescent brain maturation. J Neurosci 21:8819–8829
Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW (2003) Mapping cortical change across the human life span. Nat Neurosci 6:309–315
Spear LP (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463
Stalnaker TA, Takahashi Y, Roesch MR, Schoenbaum G (2009) Neural substrates of cognitive inflexibility after chronic cocaine exposure. Neuropharmacology 56(Suppl 1):63–72
Stefani MR, Groth K, Moghaddam B (2003) Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability. Behav Neurosci 117:728–737
Tanabe J, Tregellas JR, Dalwani M, Thompson L, Owens E, Crowley T, Banich M (2009) Medial orbitofrontal cortex gray matter is reduced in abstinent substance-dependent individuals. Biol Psychiatry 65:160–164
Thai CA, Zhang Y, Howland JG (2013) Effects of acute restraint stress on set-shifting and reversal learning in male rats. Cogn Affect Behav Neurosci 13:164–173
van der Plas EA, Crone EA, van den Wildenberg WP, Tranel D, Bechara A (2009) Executive control deficits in substance-dependent individuals: a comparison of alcohol, cocaine, and methamphetamine and of men and women. J Clin Exp Neuropsychol 31:706–719
van Gorp WG, Wilkins JN, Hinkin CH, Moore LH, Hull J, Horner MD, Plotkin D (1999) Declarative and procedural memory functioning in abstinent cocaine abusers. Arch Gen Psychiatry 56:85–89
Volkow ND, Hitzemann R, Wang GJ, Fowler JS, Wolf AP, Dewey SL, Handlesman L (1992) Long-term frontal brain metabolic changes in cocaine abusers. Synapse 11:184–190
Williams J, Pacula RL, Chaloupka FJ, Wechsler H (2006) College students’ use of cocaine. Subst Use Misuse 41:489–509
Winstanley CA, LaPlant Q, Theobald DE, Green TA, Bachtell RK, Perrotti LI, DiLeone RJ, Russo SJ, Garth WJ, Self DW, Nestler EJ (2007) DeltaFosB induction in orbitofrontal cortex mediates tolerance to cocaine-induced cognitive dysfunction. J Neurosci 27:10497–10507
Winter S, Dieckmann M, Schwabe K (2009) Dopamine in the prefrontal cortex regulates rats behavioral flexibility to changing reward value. Behav Brain Res 198:206–213
Woicik PA, Moeller SJ, Alia-Klein N, Maloney T, Lukasik TM, Yeliosof O, Wang GJ, Volkow ND, Goldstein RZ (2009) The neuropsychology of cocaine addiction: recent cocaine use masks impairment. Neuropsychopharmacology 34:1112–1122
Woicik PA, Urban C, Alia-Klein N, Henry A, Maloney T, Telang F, Wang GJ, Volkow ND, Goldstein RZ (2011) A pattern of perseveration in cocaine addiction may reveal neurocognitive processes implicit in the Wisconsin Card Sorting Test. Neuropsychologia 49:1660–1669
Wydra K, Golembiowska K, Zaniewska M, Kaminska K, Ferraro L, Fuxe K, Filip M (2013) Accumbal and pallidal dopamine, glutamate and GABA overflow during cocaine self-administration and its extinction in rats. Addict Biol 18:307–324
Zink CF, Tong Y, Chen Q, Bassett DS, Stein JL, Meyer-Lindenberg A (2008) Know your place: neural processing of social hierarchy in humans. Neuron 58:273–283
Acknowledgments
This research was supported by NSF grant SMA 0835976 to the CELEST Science of Learning Center (B. Shinn-Cunningham, PI).
Conflict of interest
The authors declare no conflicts of interest. Experiments comply with the current laws of the country in which they were performed.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kantak, K.M., Barlow, N., Tassin, D.H. et al. Performance on a strategy set shifting task in rats following adult or adolescent cocaine exposure. Psychopharmacology 231, 4489–4501 (2014). https://doi.org/10.1007/s00213-014-3598-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-014-3598-y