Skip to main content
SpringerLink
Log in

Perinatal Treatments with the Dopamine D2-Receptor Agonist Quinpirole Produces Permanent D2-Receptor Supersensitization: a Model of Schizophrenia

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Repeated daily treatments of perinatal rats with the dopamine D2-receptor (D2-R) agonist quinpirole for a week or more produces the phenomenon of ‘priming’—gradual but long-term sensitization of D2-R. In fact a daily dose of quinpirole as low as 50 µg/kg/day is adequate for sensitizing D2-R. Primed rats as neonates and in adolescence, when acutely treated with quinpirole display enhanced eating/gnawing/nursing on dams, also horizontal locomotor activity. Between 3 and 5 weeks of age, acute quinpirole treatment of primed rats produces profound vertical jumping with paw treading—a behavior that is not observed in control rats. At later ages acute quinpirole treatment is associated with enhanced yawning, a D2-R-associated behavior. This long-term D2-R supersensitivity is believed to be life-long, despite the relatively brief period of D2-R priming near the time of birth. D2-R supersensitivity is not associated with an increase in the number or affinity of D2-R, as assessed in the striatum of rats; nor is it induced with the D3-R agonist 7-OH-DPAT. However, quinpirole-induced D2-R supersensitivity is associated with cognitive deficits, also a deficit in pre-pulse inhibition and in neurotrophic factors, and low levels of the transcript regulator of G-protein signaling (RGS) RGS9 in brain; and acute reversal of these alterations by the antipsychotic agent olanzapine. In sum, rats ontogenetically D2-R supersensitized have face validity, construct validity and predictive ability for schizophrenia.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kostrzewa JP, Kostrzewa RA, Kostrzewa RM, Brus R, Nowak P (2016) Perinatal 6-hydroxydopamine modeling of ADHD. In: Kostrzewa RM, Archer T (eds) Current topics in behavioral neuroscience. Springer, New York (in press)

  2. Brown RW, Maple AM, Perna MK, Sheppard AB, Cope ZA, Kostrzewa RM (2012) Schizophrenia and substance abuse comorbidity: nicotine addiction and the neonatal quinpirole model. Dev Neurosci 34(2–3):140–151

    Article  CAS  PubMed  Google Scholar 

  3. Maple AM, Smith KJ, Perna MK, Brown RW (2015) Neonatal quinpirole treatment produces prepulse inhibition deficits in adult male and female rats. Pharmacol Biochem Behav 137:93–100

    Article  CAS  PubMed  Google Scholar 

  4. Kostrzewa JP, Kostrzewa RA, Kostrzewa RM, Brus R, Nowak P (2016) Perinatal 6-hydroxydopamine to produce a life-long model of severe Parkinson’s disease. In: Kostrzewa RM, Archer T (eds) Current topics in behavioral neuroscience. Springer, New York (in press)

  5. Kostrzewa RM, JP Kostrzewa, R Brus (2014) Tardive dyskinesia: Outcome of antipsychotic treatment and brain damage?, in section on diseases and disorders relevant to neurotoxins. In: Kostrzewa RM (ed) Handbook of neurotoxicity. Springer, New York, pp 2315–2326. ISBN 978-1-4614-5835-7 (print); ISBN 978-1-4614-5836-4 (eBook); ISBN 978-1-4614-7458-6 (print and electronic bundle). doi:10.1007/978-1-4614-5836-4_163

  6. Kostrzewa RM, Brus R (2016) Life-long Rodent Model of Tardive Dyskinesia—persistence after antipsychotic drug withdrawal. In: Kostrzewa RM, Archer T (eds) Current topics in behavioral neuroscience. Springer, New York (in press)

  7. Kostrzewa RM (1995) Dopamine receptor supersensitivity. Neurosci Biobehav Rev 19(1):1–17. (Review)

  8. Clow A, Theodorou A, Jenner P, Marsden CD (1980) A comparison of striatal and mesolimbic dopamine function in the rat during 6-month trifluoperazine administration. Psychopharmacology 69(3):227–233

    Article  CAS  PubMed  Google Scholar 

  9. Dewey KJ, Fibiger HC (1983) The effects of dose and duration of chronic pimozide administration on dopamine receptor supersensitivity. Naunyn Schmiedebergs Arch Pharmacol 322(4):261–270

    Article  CAS  PubMed  Google Scholar 

  10. Breese GR, Baumeister AA, McCown TJ, Emerick SG, Frye GD, Crotty K, Mueller RA (1984) Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine. J Pharmacol Exp Ther 231(2):343–354

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Breese GR, Baumeister A, Napier TC, Frye GD, Mueller RA (1985) Evidence that D-1 dopamine receptors contribute to the supersensitive behavioral responses induced by l-dihydroxyphenylalanine in rats treated neonatally with 6-hydroxydopamine. J Pharmacol Exp Ther 235(2):287–295

    CAS  PubMed  Google Scholar 

  12. Breese GR, Napier TC, Mueller RA (1985) Dopamine agonist-induced locomotor activity in rats treated with 6-hydroxydopamine at differing ages: functional supersensitivity of D-1 dopamine receptors in neonatally lesioned rats. J Pharmacol Exp Ther 234(2):447–455

    CAS  PubMed  Google Scholar 

  13. Breese GR, Duncan GE, Napier TC, Bondy SC, Iorio LC, Mueller RA (1987) 6-hydroxydopamine treatments enhance behavioral responses to intracerebral microinjection of D1- and D2-dopamine agonists into nucleus accumbens and striatum without changing dopamine antagonist binding. J Pharmacol Exp Ther 240(1):167–176

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Criswell H, Mueller RA, Breese GR (1989) Priming of D1-dopamine receptor responses: long-lasting behavioral supersensitivity to a D1-dopamine agonist following repeated administration to neonatal 6-OHDA-lesioned rats. J Neurosci 9(1):125–133

    CAS  PubMed  Google Scholar 

  15. Kostrzewa RM, Gong L (1991) Supersensitized D1 receptors mediate enhanced oral activity after neonatal 6-OHDA. Pharmacol Biochem Behav 39(3):677–682

    Article  CAS  PubMed  Google Scholar 

  16. Kostrzewa RM, Hamdi A, Kostrzewa FP (1990) Production of prolonged supersensitization of dopamine D2 receptors. Eur J Pharmacol 183:1411–1412

    Article  Google Scholar 

  17. Brus R, Szkilnik R, Nowak P, Kasperska A, Oswiecimska J, Kostrzewa R, Shani J (1998) Locomotor sensitization of dopamine receptors by their agonists quinpirole and SKF-38393, during maturation and aging in rats. Pharmacol Rev Commun 10:25–30

    CAS  Google Scholar 

  18. Brus R, Szkilnik R, Nowak P, Kostrzewa R, Shani J (1998) Sensitivity of central dopamine receptors in rats to quinpirole and SKF-38393, administered at their early stages of ontogenicity, evaluated by learning and memorizing a conditioned avoidance reflex. Pharmacol Rev Commun 10:31–36

    CAS  Google Scholar 

  19. Eilam D, Szechtman H (1990) Dosing regimen differentiates sensitization of locomotion and mouthing to D2 agonist quinpirole. Pharmacol Biochem Behav 36(4):989–991

    Article  CAS  PubMed  Google Scholar 

  20. Einat H, Szechtman H (1993) Environmental modulation of both locomotor response and locomotor sensitization to the dopamine agonist quinpirole. Behav Pharmacol 4(4):399–403

    Article  CAS  PubMed  Google Scholar 

  21. Einat H, Szechtman H (1993) Longlasting consequences of chronic treatment with the dopamine agonist quinpirole for the undrugged behavior of rats. Behav Brain Res 54(1):35–41

    Article  CAS  PubMed  Google Scholar 

  22. Einat H, Einat D, Allan M, Talangbayan H, Tsafnat T, Szechtman H (1996) Associational and nonassociational mechanisms in locomotor sensitization to the dopamine agonist quinpirole. Psychopharmacology 127(2):95–101

    Article  CAS  PubMed  Google Scholar 

  23. Mogilnicka E, Klimek V (1977) Drugs affecting dopamine neurons and yawning behavior. Pharmacol Biochem Behav 7(4):303–305

    Article  CAS  PubMed  Google Scholar 

  24. Gower AJ, Berendsen HG, Princen MM, Broekkamp CL (1984) The yawning-penile erection syndrome as a model for putative dopamine autoreceptor activity. Eur J Pharmacol 103(1–2):81–89

    Article  CAS  PubMed  Google Scholar 

  25. Longoni R, Spina L, Di Chiara G (1987) Permissive role of D-1 receptor stimulation by endogenous dopamine for the expression of postsynaptic D-2-mediated behavioural responses. Yawning in rats. Eur J Pharmacol 134(2):163–173

    Article  CAS  PubMed  Google Scholar 

  26. Serra G, Collu M, Gessa GL (1987) Yawning is elicited by D2 dopamine agonists but is blocked by the D1 antagonist, SCH 23390. Psychopharmacology 91(3):330–333

    Article  CAS  PubMed  Google Scholar 

  27. Yamada K, Nagashima M, Kimura H, Matsumoto S, Furukawa T (1990) Possible involvement of differing classes of dopamine D-2 receptors in yawning and stereotypy in rats. Psychopharmacology 100(2):141–144

    Article  CAS  PubMed  Google Scholar 

  28. Kostrzewa RM, Brus R (1991) Ontogenic homologous supersensitization of quinpirole-induced yawning in rats. Pharmacol Biochem Behav 39(2):517–519

    Article  CAS  PubMed  Google Scholar 

  29. Plech A, Brus R, Kalbfleisch JH, Kostrzewa RM (1995) Enhanced oral activity responses to intrastriatal SKF 38393 and m-CPP are attenuated by intrastriatal mianserin in neonatal 6-OHDA-lesioned rats. Psychopharmacology 119:466–473

    Article  CAS  PubMed  Google Scholar 

  30. Kostrzewa RM, Brus R, Rykaczewska M, Plech A (1993) Low-dose quinpirole ontogenically sensitizes to quinpirole-induced yawning in rats. Pharmacol Biochem Behav 44(2):487–489

    Article  CAS  PubMed  Google Scholar 

  31. Kostrzewa RM, Guo J, Kostrzewa FP (1993) Ontogenetic quinpirole treatment induces vertical jumping activity in rats. Eur J Pharmacol 239(1–3):183–187

    Article  CAS  PubMed  Google Scholar 

  32. Brus R, Kostrzewa RM, Nowak P, Perry KW, Kostrzewa JP (2003) Ontogenetic quinpirole treatments fail to prime for D2 agonist-enhancement of locomotor activity in 6-hydroxydopamine-lesioned rats. Neurotoxicity Res. 5(5):329–338

    Article  Google Scholar 

  33. Paalzow GH, Paalzow LK (1983) Yohimbine both increases and decreases nociceptive thresholds in rats: evaluation of the dose-response relationship. Naunyn Schmiedebergs Arch Pharmacol 322(3):193–197

    Article  CAS  PubMed  Google Scholar 

  34. Michael-Titus A, Bousselmame R, Costentin J (1990) Stimulation of dopamine D2 receptors induces an analgesia involving an opioidergic but non enkephalinergic link. Eur J Pharmacol 187(2):201–207

    Article  CAS  PubMed  Google Scholar 

  35. Kostrzewa RM, Brus R, Kalbfleisch J (1991) Ontogenetic homologous sensitization to the antinociceptive action of quinpirole in rats. Eur J Pharmacol 209(3):157–161

    Article  CAS  PubMed  Google Scholar 

  36. Brown RW, Flanigan TJ, Thompson KN, Thacker SK, Schaefer TL, Williams MT (2004) Neonatal quinpirole treatment impairs Morris water task performance in early postweanling rats: relationship to increases in corticosterone and decreases in neurotrophic factors. Biol Psychiatry 56(3):161–168

    Article  CAS  PubMed  Google Scholar 

  37. Brown RW, Thompson KN, Click IA, Best RA, Thacker SK, Perna MK (2005) The effects of eticlopride on Morris water task performance in male and female rats neonatally treated with quinpirole. Psychopharmacology 180(2):234–240

    Article  CAS  PubMed  Google Scholar 

  38. Thacker SK, Perna MK, Ward JJ, Schaefer TL, Williams MT, Kostrzewa RM, Brown RW (2006) The effects of adulthood olanzapine treatment on cognitive performance and neurotrophic factor content in male and female rats neonatally treated with quinpirole. Eur J Neurosci 24(7):2075–2083

    Article  PubMed  Google Scholar 

  39. Brown RW, Gass JT, Kostrzewa RM (2002) Ontogenetic quinpirole treatments produce spatial memory deficits and enhance skilled reaching in adult rats. Pharmacol Biochem Behav 72(3):591–600

    Article  CAS  PubMed  Google Scholar 

  40. Andersen SL, Teicher MH (2000) Sex differences in dopamine receptors and their relevance to ADHD. Neurosci Biobehav Rev 24(1):137–141

    Article  CAS  PubMed  Google Scholar 

  41. Sheppard B, Lehmann J, Cope ZA, Brown RW (2009) Sex differences in nicotine sensitization and conditioned hyperactivity in adolescent rats neonatally treated with quinpirole: role of D2 and D3 receptor subtypes. Behav Neurosci 123(6):1296–1308

    Article  CAS  PubMed  Google Scholar 

  42. Perna MK, Cope ZA, Maple AM, Longacre ID, Correll JA, Brown RW (2008) Nicotine sensitization in adult male and female rats quinpirole-primed as neonates. Psychopharmacology 199(1):67–75 Epub 2008 Jun 12

    Article  CAS  PubMed  Google Scholar 

  43. Maple AM, Perna MK, Parlaman JP, Stanwood GD, Brown RW (2007) Ontogenetic quinpirole treatment produces long-lasting decreases in the expression of Rgs9, but increases Rgs17 in the striatum, nucleus accumbens and frontal cortex. Eur J Neurosci 26(9):2532–2538

    Article  PubMed  Google Scholar 

  44. Kostrzewa RM, Brus R (1991) Is dopamine-agonist induced yawning behavior a D3 mediated event? Life Sci 48(26):PL129

    Article  CAS  PubMed  Google Scholar 

  45. Oswiecimska J, Brus R, Szkilnik R, Nowak P, Kostrzewa RM (2000) 7-OH-DPAT, unlike quinpirole, does not prime a yawning response in rats. Pharmacol Biochem Behav 67(1):11–15

    Article  CAS  PubMed  Google Scholar 

  46. Seeman P, Ko F, Jack E, Greenstein R, Dean B (2007) Consistent with dopamine supersensitivity, RGS9 expression is diminished in the amphetamine-treated animal model of schizophrenia and in postmortem schizophrenia brain. Synapse 61:303–309

    Article  CAS  PubMed  Google Scholar 

  47. Rahman Z, Schwarz J, Gold SJ, Zachariou V, Wein MN, Choi KH, Kovoor A, Chen CK, DiLeone RJ, Schwarz SC, Selley DE, Sim-Selley LJ, Barrot M, Luedtke RR, Self D, Neve RL, Lester HA, Simon MI, Nestler EJ (2003) RGS9 modulates dopamine signaling in the basal ganglia. Neuron 38:941–952

    Article  CAS  PubMed  Google Scholar 

  48. James MA, Lu Y, Liu Y, Vikis HG, You M (2009) RGS17, an overexpressed gene in human lung and prostate cancer, induces tumor cell proliferation through the cyclic AMP-PKA-CREB pathway. Cancer Res 69(5):2108–2116 (Epub 2009 Feb 24)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Levitt P, Ebert P, Mirnics K, Nimgaonkar VL, Lewis DA (2006) Making the case for a candidate Vulnerability gene in schizophrenia: convergent evidence for regulator of G-protein signaling 4 (RGS4). Biol Psychiatry 60:534–537

    Article  CAS  PubMed  Google Scholar 

  50. Ding L, Hegde AN (2009) Expression of RGS4 splice variants in dorsolateral prefrontal cortex of schizophrenic and bipolar disorder patients. Biol Psychiatry 65(6):541–545

    Article  CAS  PubMed  Google Scholar 

  51. Jönsson EG, Saetre P, Nyholm H, Djurovic S, Melle I, Andreassen OA, Skjødt C, Thygesen JH, Werge T, Hall H, Agartz I, Terenius L (2012) Lack of association between the regulator of G-protein signaling 4 (RGS4) rs951436 polymorphism and schizophrenia. Psychiatr Genet 22(5):263–264

    Article  PubMed  Google Scholar 

  52. Nowak P, Brus R, Kostrzewa RM (2001) Amphetamine-induced enhancement of neostriatal in vivo microdialysate dopamine content in rats, quinpirole-primed as neonates. Pol J Pharmacol 53(4):319–329

    CAS  PubMed  Google Scholar 

  53. Seutin V, Verbanck P, Massotte L, Dresse A (1991) Acute amphetamine-induced subsensitivity of A10 dopamine autoreceptors in vitro. Brain Res 558:141–144

    Article  CAS  PubMed  Google Scholar 

  54. Marinelli M, Cooper DC, Baker LK, White FJ (2003) Impulse activity of midbrain dopamine neurons modulates drug-seeking behavior. Psychopharmacology 168:84–98 (Erratum in: Psychopharmacology 170:334)

    Article  CAS  PubMed  Google Scholar 

  55. Tammimäki A, Pietilä K, Raattamaa H, Ahtee L (2006) Effect of quinpirole on striatal dopamine release and locomotor activity in nicotine-treated mice. Eur J Pharmacol 531:118–125

    Article  PubMed  Google Scholar 

  56. Karkhanis AN, Rose JH, Huggins KN, Konstantopoulos JK, Jones SR (2015) Chronic intermittent ethanol exposure reduces presynaptic dopamine neurotransmission in the mouse nucleus accumbens. Drug Alcohol Depend 150:24–30

    Article  CAS  PubMed  Google Scholar 

  57. Sara GE, Large MM, Matheson SL, Burgess PM, Malhi GS, Whiteford HA, Hall WD (2015) Stimulant use disorders in people with psychosis: a meta-analysis of rate and factors affecting variation. Aust N Z J Psychiatry 49:106–117

    Article  PubMed  Google Scholar 

  58. Brus R, Szkilnik R, Kostrzewa R (1997) Quinpirole-induced yawning behavior in rats neonatally pretreated with 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytryptamine (5,7-DHT). Med Sci Monit 3:324–327

    CAS  Google Scholar 

  59. Kostrzewa RM, Kostrzewa FP (2012) Neonatal 6-hydroxydopamine lesioning enhances quinpirole- induced vertical jumping in rats that were quinpirole-primed during postnatal ontogeny. Neurotox Res 21(2):231–235

    Article  CAS  PubMed  Google Scholar 

  60. Kostrzewa RM, Kostrzewa JP, Nowak P, Kostrzewa RA, Brus R (2004) Dopamine D2 agonist priming in intact and dopamine-lesioned rats. Neurotox Res 6(6):457–462

    Article  PubMed  Google Scholar 

  61. Nowak P, Labus Ł, Kostrzewa RM, Brus R (2006) DSP-4 prevents dopamine receptor priming by quinpirole. Pharmacol Biochem Behav 84(1):3–7 (Epub 2006 May 3)

    Article  CAS  PubMed  Google Scholar 

  62. Nowak P, Nitka D, Kwieciński A, Jośko J, Drab J, Pojda-Wilczek D, Kasperski J, Kostrzewa RM, Brus R (2009) Neonatal co-lesion by DSP-4 and 5,7-DHT produces adulthood behavioral sensitization to dopamine D(2) receptor agonists. Pharmacol Rep 61(2):311–318

    Article  CAS  PubMed  Google Scholar 

  63. Tizabi Y, Copeland RL Jr, Brus R, Kostrzewa RM (1999) Nicotine blocks quinpirole-induced behavior in rats: psychiatric implications. Psychopharmacology 145:433–441

    Article  CAS  PubMed  Google Scholar 

  64. Richardson SA, Tizabi Y (1994) Hyperactivity in the offspring of nicotine-treated rats: role of the mesolimbic and nigrostriatal dopaminergic pathways. Pharmacol Biochem Behav 47(2):331–337

    Article  CAS  PubMed  Google Scholar 

  65. Freedman R, Adams CE, Leonard S (2000) The alpha7-nicotinic acetylcholine receptor and the pathology of hippocampal interneurons in schizophrenia. Chem Neuroanat 20:299–306

    Article  CAS  Google Scholar 

  66. Brown RW, Thompson KD, Thompson KN, Ward JJ, Thacker SK, Williams MT, Kostrzewa RM (2004) Adulthood nicotine treatment alleviates behavioural impairments in rats neonatally treated with quinpirole: possible roles of acetylcholine function and neurotrophic factor expression. Eur J Neurosci 19(6):1634–1642

    Article  PubMed  Google Scholar 

  67. Brown RW, Perna MK, Schaefer TL, Williams MT (2006) The effects of adulthood nicotine treatment on D2-mediated behavior and neurotrophins of rats neonatally treated with quinpirole. Synapse 59(5):253–259

    Article  CAS  PubMed  Google Scholar 

  68. Moore H, West AR, Grace AA (1999) The regulation of forebrain dopamine transmission: relevance to the pathophysiology and psychopathology of schizophrenia. Biol Psychiatry 46(1):40–55

    Article  CAS  PubMed  Google Scholar 

  69. Karam CS, Ballon JS, Bivens NM, Freyberg Z, Girgis RR, Lizardi-Ortiz JE, Markx S, Lieberman JA, Javitch JA (2010) Signaling pathways in schizophrenia: emerging targets and therapeutic strategies. Trends Pharmacol Sci 31(8):381–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Cotter D, Pariante CM (2002) Stress and the progression of the developmental hypothesis of schizophrenia. Br J Psychiatry 181:363–365

    Article  PubMed  Google Scholar 

  71. Crook JM, Tomaskovic-Crook E, Copolov DL, Dean B (2001) Low muscarinic receptor binding in prefrontal cortex from subjects with schizophrenia: a study of Brodmann’s areas 8, 9, 10, and 46 and the effects of neuroleptic drug treatment. Am J Psychiatry 158:918–925

    Article  CAS  PubMed  Google Scholar 

  72. Leonard S, Gault J, Hopkins J, Logel J, Vianzon R, Short M, Drebing C, Berger R, Venn D, Sirota P, Zerbe G, Olincy A, Ross RG, Adler LE, Freedman R (2002) Association of promoter variants in the alpha7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found. Arch Gen Psychiatry 59:1085–1096

    Article  CAS  PubMed  Google Scholar 

  73. Mäki P, Veijola J, Jones PB, Murray GK, Koponen H, Tienari P, Miettunen J, Tanskanen P, Wahlberg KE, Koskinen J, Lauronen E, Isohanni M (2005) Predictors of schizophrenia–a review. Br Med Bull 73–74:1–15

    Article  PubMed  Google Scholar 

  74. Monteiro P, Feng G (2015) Learning from animal models of obsessive-compulsive disorder. Biol Psychiatry. doi:10.1016/j.biopsych.2015.04.020

  75. Nowakowska E, Kus K, Ratajczak P, Cichocki M, Woźniak A (2014) The influence of aripiprazole, olanzapine and enriched environment on depressant-like behavior, spatial memory dysfunction and hippocampal level of BDNF in prenatally stressed rats. Pharmacol Rep 66(3):404–411

    Article  CAS  PubMed  Google Scholar 

  76. Rizos EN, Papadopoulou A, Laskos E, Michalopoulou PG, Kastania A, Vasilopoulos D, Katsafouros K, Lykouras L (2010) Reduced serum BDNF levels in patients with chronic schizophrenic disorder in relapse, who were treated with typical or atypical antipsychotics. World J Biol Psychiatry 11(2 Pt 2):251–255

    Article  PubMed  Google Scholar 

  77. Zhang C, Fang Y, Xu L (2014) Glutamate receptor 1 phosphorylation at serine 845 contributes to the therapeutic effect of olanzapine on schizophrenia-like cognitive impairments. Schizophr Res 159(2–3):376–384

    Article  PubMed  Google Scholar 

  78. Thoma P, Daum I (2013) Comorbid substance use disorder in schizophrenia: a selective overview of neurobiological and cognitive underpinnings. Psychiatry Clin Neurosci 67(6):367–383

    Article  PubMed  Google Scholar 

  79. McCreadie RG, Kelly C (2000) Patients with schizophrenia who smoke. Private disaster, public resource. Br J Psychiatry 176:109

    Article  CAS  PubMed  Google Scholar 

  80. Cope ZA, Huggins KN, Sheppard AB, Noel DM, Roane DS, Brown RW (2010) Neonatal quinpirole treatment enhances locomotor activation and dopamine release in the nucleus accumbens core in response to amphetamine treatment in adulthood. Synapse 64(4):289–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D’Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB (1996) Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci USA 93(17):9235–9240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Balu DT, Coyle JT (2015) The NMDA receptor ‘glycine modulatory site’ in schizophrenia: d-serine, glycine, and beyond. Curr Opin Pharmacol 20:109–115

    Article  CAS  PubMed  Google Scholar 

  83. Meltzer HY, Rajagopal L, Huang M, Oyamada Y, Kwon S, Horiguchi M (2013) Translating the N-methyl-d-aspartate receptor antagonist model of schizophrenia to treatments for cognitive impairment in schizophrenia. Int J Neuropsychopharmacol 16(10):2181–2194

    Article  CAS  PubMed  Google Scholar 

  84. Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB (2015) Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry 2(3):258–270. doi:10.1016/S2215-0366(14)00122-9 (Epub 2015 Feb 25. Review)

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA

    Richard M. Kostrzewa & Russell W. Brown

  2. Department of Toxicology and Occupational Health Protection, Public Health Faculty, Medical University of Silesia, 40-752, Katowice Ligota, Poland

    Przemysław Nowak

  3. Department of Nurse, High School of Strategic Planning, 41-303, Dabrowa Gornicza, Poland

    Ryszard Brus

Authors
  1. Richard M. Kostrzewa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Przemysław Nowak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryszard Brus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Russell W. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard M. Kostrzewa.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kostrzewa, R.M., Nowak, P., Brus, R. et al. Perinatal Treatments with the Dopamine D2-Receptor Agonist Quinpirole Produces Permanent D2-Receptor Supersensitization: a Model of Schizophrenia. Neurochem Res 41, 183–192 (2016). https://doi.org/10.1007/s11064-015-1757-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-015-1757-0

Keywords

Search

Navigation