Skip to main content

Advertisement

Log in

Stimulation of D2 receptors in the prefrontal cortex reduces PCP-induced hyperactivity, acetylcholine release and dopamine metabolism in the nucleus accumbens

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

The aim of the present study was to investigate the effects of stimulation of D2 receptors in the prefrontal cortex (PFC) on spontaneous motor activity and the hyperactivity induced by the psychomimetic phencyclidine (PCP). In addition, the effects of prefrontal D2 stimulation under PCP treatment on dialysate concentrations of acetylcholine, choline, dopamine, DOPAC and HVA in the nucleus accumbens were also investigated. Sprague-Dawley male rats were implanted with guide cannulae to perform bilateral injections into the medial PFC of the D2 agonist quinpirole (1.5 and 5 µg/side). Horizontal and vertical spontaneous motor activity and the motor activity induced by systemic injections of the PCP (5 mg/kg i.p.) were monitored in the open field. PFC injections of quinpirole (1.5 and 5 µg/side) significantly decreased horizontal and vertical spontaneous motor activity in a dose-related manner. These effects were blocked by the D2 antagonist raclopride (5 µg/side). Microinjections of quinpirole (1.5 and 5 µg/side) into the PFC also significantly attenuated the hyperactivity produced by PCP (5 mg/kg i.p.). PCP also increased dialysate concentrations of acetylcholine, and dopamine metabolites in the nucleus accumbens. These increases were also reduced by injections of quinpirole (5 µg/side) into the PFC. These results suggest that the stimulation of prefrontal D2 receptors plays an inhibitory role in regulating spontaneous and PCP-induced motor activity and also in the neurochemical changes produced by PCP in the nucleus accumbens.

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

Access this article

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

  • S Ahlenius V Hillegaart G Thorell O Magnusson CJ Fowler (1987) ArticleTitleSupression of exploratory locomotor activity and increase in dopamine turnover following the local application of cis-flupenthixol into limbic projection areas of the rat striatum Brain Res 402 131–138 Occurrence Handle3828778 Occurrence Handle10.1016/0006-8993(87)91055-9 Occurrence Handle1:CAS:528:DyaL2sXhtFenu7o%3D

    Article  PubMed  CAS  Google Scholar 

  • T Bast MA Pezze J Feldon (2002) ArticleTitleDopamine receptor blockade in the rat medial prefrontal cortex reduces spontaneous and amphetamine-induced activity and does not affect prepulse inhibition Behav Pharmacol 13 669–673 Occurrence Handle12478219 Occurrence Handle1:CAS:528:DC%2BD38XpsVSrsLs%3D

    PubMed  CAS  Google Scholar 

  • M Bentivoglio M Morelli (2005) The organization and circuits of mesencephalic dopaminergic neurons and the distribution of dopamine receptors in the brain Elsevier B.V. Dopamine 1–107

    Google Scholar 

  • CE Beyer JD Steketee (2000) ArticleTitleIntra-medial prefrontal cortex injection of quinpirole, but not SKF 38393, blocks the acute motor-stimulant response to cocaine in the rat Psychopharmacology 151 211–218 Occurrence Handle10972467 Occurrence Handle10.1007/s002139900345 Occurrence Handle1:CAS:528:DC%2BD3cXmtFyks7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • CE Beyer JD Steketee (2001) ArticleTitleCharacterization of the role of medial prefrontal cortex dopamine receptors in cocaine-induced locomotor activity Behav Neurosci 115 1093–1100 Occurrence Handle11584922 Occurrence Handle10.1037/0735-7044.115.5.1093 Occurrence Handle1:CAS:528:DC%2BD3MXnsFWmtr4%3D

    Article  PubMed  CAS  Google Scholar 

  • LM Broersen J Feldon I Weiner (1999) ArticleTitleDissociative effects of apomorphine infusions into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine-induced locomotion Neuroscience 94 39–46 Occurrence Handle10613495 Occurrence Handle10.1016/S0306-4522(99)00287-0 Occurrence Handle1:CAS:528:DyaK1MXlvVWntb8%3D

    Article  PubMed  CAS  Google Scholar 

  • DB Carr SR Sesack (2000) ArticleTitleProjections from the rat prefrontal cortex to the ventral tegmental area: target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons J Neurosci 20 3864–3873 Occurrence Handle10804226 Occurrence Handle1:CAS:528:DC%2BD3cXjtlKqsbY%3D

    PubMed  CAS  Google Scholar 

  • PB Clarke A Jakubovic HC Fibiger (1988) ArticleTitleAnatomical analysis of the involvement of mesolimbocortical dopamine in the locomotor stimulant actions of d-amphetamine and apomorphine Psychopharmacology 96 511–520 Occurrence Handle3149775 Occurrence Handle10.1007/BF02180033 Occurrence Handle1:CAS:528:DyaL1MXjtlKrtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • M de Rover JC Lodder KS Kits AN Schoffelmeer AB Brussaard (2002) ArticleTitleCholinergic modulation of nucleus accumbens medium spiny neurons Eur J Neurosci 16 2279–2290 Occurrence Handle12492422 Occurrence Handle10.1046/j.1460-9568.2002.02289.x

    Article  PubMed  Google Scholar 

  • A Del Arco F Mora (1999) ArticleTitleEffects of endogenous glutamate on extracellular concentrations of GABA, dopamine and dopamine metabolites in the prefrontal cortex of the freely moving rat: involvement of NMDA and AMPA/kainate receptors Neurochem Res 24 1027–1035 Occurrence Handle10478942 Occurrence Handle10.1023/A:1021056826829 Occurrence Handle1:CAS:528:DyaK1MXlsVOktbY%3D

    Article  PubMed  CAS  Google Scholar 

  • A Del Arco F Mora (2005) ArticleTitleGlutamate-dopamine in vivo interaction in the prefrontal cortex modulates the release of dopamine and acetylcholine in the nucleus accumbens of the awake rat J Neural Transm 112 97–109 Occurrence Handle15599608 Occurrence Handle10.1007/s00702-004-0172-5 Occurrence Handle1:CAS:528:DC%2BD2cXhtVKrur%2FN

    Article  PubMed  CAS  Google Scholar 

  • A Del Arco Z Shunwei A Teraasma AH Mohammed K Fuxe (2004) ArticleTitleHyperactivity to novelty induced by social isolation is not correlated with changes in D2 receptor function and binding in striatum Psychopharmacology 171 148–155 Occurrence Handle13680076 Occurrence Handle10.1007/s00213-003-1578-8 Occurrence Handle1:CAS:528:DC%2BD3sXhtVSjsLnP

    Article  PubMed  CAS  Google Scholar 

  • AY Deutch SY Tam AS Freeman MB Bowers RH Roth (1987) ArticleTitleMesolimbic and mesocortical dopamine-activation induced by phencyclidine: contrasting pattern to striatal response Eur J Pharmacol 134 257–264 Occurrence Handle3569414 Occurrence Handle10.1016/0014-2999(87)90356-6 Occurrence Handle1:STN:280:DyaL2s7ptVOhtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • MD Doherty A Gratton (1996) ArticleTitleMedial prefrontal cortical D1 receptor modulation of the meso-accumbens dopamine response to stress: an electrochemical study in freely-behaving rats Brain Res 715 86–97 Occurrence Handle8739626 Occurrence Handle10.1016/0006-8993(95)01557-4 Occurrence Handle1:CAS:528:DyaK28Xisl2lsLo%3D

    Article  PubMed  CAS  Google Scholar 

  • RJ Dolan P Fletcher CD Frith KJ Friston RS Frackowiak PM Grasby (1995) ArticleTitleDopaminergic modulation of impaired cognitive activation in the anterior cingulate cortex in schizophrenia Nature 378 180–182 Occurrence Handle7477319 Occurrence Handle10.1038/378180a0 Occurrence Handle1:CAS:528:DyaK2MXptlSmtLs%3D

    Article  PubMed  CAS  Google Scholar 

  • CL Duvauchelle M Levitin LA MacConell LK Lee A Ettenberg (1992) ArticleTitleOpposite effects of prefrontal cortex and nucleus accumbens infusions of flupenthixol on stimulant-induced locomotion and brain stimulation reward Brain Res 576 104–110 Occurrence Handle1515903 Occurrence Handle10.1016/0006-8993(92)90614-F Occurrence Handle1:CAS:528:DyaK38XisV2itLs%3D

    Article  PubMed  CAS  Google Scholar 

  • PS Goldman-Rakic EC Muly SuffixIII GV Williams (2000) ArticleTitleD1 receptors in prefrontal cells and circuits Brain Res Rev 31 295–301 Occurrence Handle10719156 Occurrence Handle10.1016/S0165-0173(99)00045-4 Occurrence Handle1:CAS:528:DC%2BD3cXhsleqtro%3D

    Article  PubMed  CAS  Google Scholar 

  • J Guo-Zhang Z Zi-Tao F Yu (2002) ArticleTitle(−)-Stepholidine: a potential novel antipsychotic drug with dual D1 receptor agonist and D2 receptor antagonist actions Trends Pharmacol Sci 23 4–7 Occurrence Handle10.1016/S0165-6147(00)01929-5

    Article  Google Scholar 

  • LF Hernández G Segovia F Mora (2003) ArticleTitleEffects of activation of NMDA and AMPA glutamate receptors on the extracellular concentrations of dopamine, acetylcholine and GABA in striatum of the awake rat: a microdialysis study Neurochem Res 28 1819–1827 Occurrence Handle14649723 Occurrence Handle10.1023/A:1026115607216

    Article  PubMed  Google Scholar 

  • T Hokfelt A Ljungdahl K Fuxe O Johansson (1974) ArticleTitleDopamine nerve terminals in the rat limbic cortex: aspects of the dopamine hypothesis of schizophrenia Science 184 177–179 Occurrence Handle4856104 Occurrence Handle10.1126/science.184.4133.177 Occurrence Handle1:CAS:528:DyaE2cXltFyhtL0%3D

    Article  PubMed  CAS  Google Scholar 

  • ME Jackson H Homayoun B Moghaddam (2004) ArticleTitleNMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex Proc Natl Acad Sci USA 101 8467–8472 Occurrence Handle15159546 Occurrence Handle10.1073/pnas.0308455101 Occurrence Handle1:CAS:528:DC%2BD2cXkvFOmtrg%3D

    Article  PubMed  CAS  Google Scholar 

  • JD Jentsch RH Roth (1999) ArticleTitleThe neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia Neuropsychopharmacology 20 201–225 Occurrence Handle10063482 Occurrence Handle10.1016/S0893-133X(98)00060-8 Occurrence Handle1:CAS:528:DyaK1MXhsleisrs%3D

    Article  PubMed  CAS  Google Scholar 

  • JD Jentsch A Tran JR Taylor RH Roth (1998) ArticleTitlePrefrontal cortical involvement in phencyclidine-induced activation of the mesolimbic dopamine system: behavioral and neurochemical evidence Psychopharmacology 138 89–95 Occurrence Handle9694531 Occurrence Handle10.1007/s002130050649 Occurrence Handle1:CAS:528:DyaK1cXkvVKksr4%3D

    Article  PubMed  CAS  Google Scholar 

  • A Kashiwa T Nishikawa K Nishijima A Umino K Takahashi (1995) ArticleTitleDizocilpine (MK-801) elicits a tetrodotoxin-sensitive increase in extracellular release of dopamine in rat medial frontal cortex Neurochem Int 26 269–279 Occurrence Handle7540467 Occurrence Handle10.1016/0197-0186(94)00125-E Occurrence Handle1:CAS:528:DyaK2MXksFyjs7g%3D

    Article  PubMed  CAS  Google Scholar 

  • K Kato T Shishido M Ono K Shishido M Kobayashi H Suzuki T Nabeshima H Furukawa S Niwa (2000) ArticleTitleEffects of phencyclidine on behavior and extracellular levels of dopamine and its metabolites in neonatal ventral hippocampal damaged rats Psychopharmacology 150 163–169 Occurrence Handle10907669 Occurrence Handle10.1007/s002130000433 Occurrence Handle1:CAS:528:DC%2BD3cXlt1Wqurs%3D

    Article  PubMed  CAS  Google Scholar 

  • PH Kelly SD Iversen (1976) ArticleTitleSelective 6OHDA-induced destruction of mesolimbic dopamine neurons: abolition of psychostimulant-induced locomotor activity in rats Eur J Pharmacol 40 45–56 Occurrence Handle1033072 Occurrence Handle10.1016/0014-2999(76)90352-6 Occurrence Handle1:CAS:528:DyaE2sXltVKrtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • SH Kim MT Price JW Olney NB Farber (1999) ArticleTitleExcessive cerebrocortical release of acetylcholine induced by NMDA antagonists is reduced by GABAergic and α2-adrenergic agonists Molecular Psychiatry 4 344–352 Occurrence Handle10483051 Occurrence Handle10.1038/sj.mp.4000529 Occurrence Handle1:CAS:528:DC%2BD3cXlvVWksro%3D

    Article  PubMed  CAS  Google Scholar 

  • D King MJ Zigmond JM Finlay (1997) ArticleTitleEffects of dopamine depletion in the medial prefrontal cortex on the stress-induced increase in extracellular dopamine in the nucleus accumbens core and shell Neuroscience 77 141–153 Occurrence Handle9044382 Occurrence Handle10.1016/S0306-4522(96)00421-6 Occurrence Handle1:CAS:528:DyaK2sXht1Wrsb0%3D

    Article  PubMed  CAS  Google Scholar 

  • JH Krystal DC D’Souza D Mathalon E Perry A Belger R Hoffman (2003) ArticleTitleNMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development Psychopharmacology 169 215–233 Occurrence Handle12955285 Occurrence Handle10.1007/s00213-003-1582-z Occurrence Handle1:CAS:528:DC%2BD3sXnvVCgtrc%3D

    Article  PubMed  CAS  Google Scholar 

  • L Lacroix LM Broersen J Feldon I Weiner (2000) ArticleTitleEffects of local infusions of dopaminergic drugs into the medial prefrontal cortex of rats on latent inhibition, prepulse inhibition and amphetamine induced activity Behav Brain Res 107 111–121 Occurrence Handle10628735 Occurrence Handle10.1016/S0166-4328(99)00118-7 Occurrence Handle1:CAS:528:DyaK1MXns1ahu7k%3D

    Article  PubMed  CAS  Google Scholar 

  • M Laruelle LS Kegeles A Abi-Dargham (2003) ArticleTitleGlutamate, dopamine, and schizophrenia. From pathophysiology to treatment Ann NY Acad Sci 1003 138–158 Occurrence Handle14684442 Occurrence Handle10.1196/annals.1300.063 Occurrence Handle1:CAS:528:DC%2BD2cXptlGrtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • MS Lidow GV Williams PS Goldman-Rakic (1998) ArticleTitleThe cerebral cortex: a case for a common site of action of antipsychotics Trends Pharmacol Sci 19 136–140 Occurrence Handle9612088 Occurrence Handle10.1016/S0165-6147(98)01186-9 Occurrence Handle1:CAS:528:DyaK1cXjt1anu74%3D

    Article  PubMed  CAS  Google Scholar 

  • A Malmberg N Mohell (1995) ArticleTitleCharacterization of (3H)quinpirole binding to human dopamine D2A and D3 receptors: effects of ions and guanine nucleotides J Pharmacol Exp Ther 274 790–797 Occurrence Handle7636742 Occurrence Handle1:CAS:528:DyaK2MXnsFSjt7w%3D

    PubMed  CAS  Google Scholar 

  • A Meyer-Lindenberg RS Miletich PD Kohn G Esposito RE Carson M Quarantelli DR Weinberger KF Berman (2002) ArticleTitleReduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia Nature Neurosci 5 267–271 Occurrence Handle11865311 Occurrence Handle10.1038/nn804 Occurrence Handle1:CAS:528:DC%2BD38XhvFKjtro%3D

    Article  PubMed  CAS  Google Scholar 

  • S Miyamoto GE Duncan CE Marx JA Lieberman (2005) ArticleTitleTreatment for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs Molecular Psychiatry 10 79–104 Occurrence Handle15289815 Occurrence Handle10.1038/sj.mp.4001556 Occurrence Handle1:CAS:528:DC%2BD2cXhtFeisL3M

    Article  PubMed  CAS  Google Scholar 

  • BJ Morris SM Cochran JA Pratt (2005) ArticleTitlePCP: from pharmacology to modelling schizophrenia Current Opinion in Pharmacology 5 101–106 Occurrence Handle15661633 Occurrence Handle10.1016/j.coph.2004.08.008 Occurrence Handle1:CAS:528:DC%2BD2MXms1Cltg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • CL Nelson JA Burk JP Bruno M Sarter (2002) ArticleTitleEffects of acute and repeated systemic administration of ketamine on prefrontal acetylcholine release and sustained attention performance in rats Psychopharmacology 161 168–179 Occurrence Handle11981597 Occurrence Handle10.1007/s00213-002-1004-7 Occurrence Handle1:CAS:528:DC%2BD38Xlt1egtrk%3D

    Article  PubMed  CAS  Google Scholar 

  • K Nishijima A Kashiwa T Nishikawa (1994) ArticleTitlePreferential stimulation of extracellular release of dopamine in rat frontal cortex to striatum following competitive inhibition of the N-methyl-D-aspartate receptor J Neurochem 63 375–378 Occurrence Handle8207441 Occurrence Handle1:CAS:528:DyaK2cXkt1Oltbc%3D Occurrence Handle10.1046/j.1471-4159.1994.63010375.x

    Article  PubMed  CAS  Google Scholar 

  • D Öngür JL Price (2000) ArticleTitleThe organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans Cerebral Cortex 10 206–219 Occurrence Handle10731217 Occurrence Handle10.1093/cercor/10.3.206

    Article  PubMed  Google Scholar 

  • G Paxinos C Watson (1998) The rat brain in stereotaxic coordinates Academic Press New York

    Google Scholar 

  • MA Pezze T Bast J Feldon (2003) ArticleTitleSignificance of dopamine transmission in the rat medial prefrontal cortex for conditioned fear Cerebral Cortex 13 371–380 Occurrence Handle12631566 Occurrence Handle10.1093/cercor/13.4.371

    Article  PubMed  Google Scholar 

  • RA Radcliffe G Erwin (1996) ArticleTitleAlterations in locomotor activity after microinjections of GBR-12909, selective dopamine antagonists or neurotensin into the medial prefrontal cortex J Pharmacol Exp Ther 277 1467–1476 Occurrence Handle8667212 Occurrence Handle1:CAS:528:DyaK28XjslGltLc%3D

    PubMed  CAS  Google Scholar 

  • TW Robbins (2000) ArticleTitleFrom arousal to cognition: integrative position of the prefrontal cortex Prog Brain Res 126 469–483 Occurrence Handle11105663 Occurrence Handle1:STN:280:DC%2BD3M%2FosFWmsA%3D%3D Occurrence Handle10.1016/S0079-6123(00)26030-5

    Article  PubMed  CAS  Google Scholar 

  • WK Schiffer M Gerasimov L Hofmann D Marsteller CR Ashby JD Brodie DL Alexoff SL Dewey (2001) ArticleTitleGamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission Neuropsychopharmacology 25 704–712 Occurrence Handle11682254 Occurrence Handle10.1016/S0893-133X(01)00268-8 Occurrence Handle1:CAS:528:DC%2BD3MXnslCjsbk%3D

    Article  PubMed  CAS  Google Scholar 

  • JK Seamans CR Yang (2004) ArticleTitleThe principal features and mechanisms of dopamine modulation in the prefrontal cortex Prog Neurobiol 74 1–57 Occurrence Handle15381316 Occurrence Handle10.1016/j.pneurobio.2004.05.006 Occurrence Handle1:CAS:528:DC%2BD2cXnslKgtr8%3D

    Article  PubMed  CAS  Google Scholar 

  • WX Shi XX Zhang (2003) ArticleTitleDendritic glutamate-induced bursting in the prefrontal cortex: further characterization and effects of phencyclidine J Pharmacol Exp Ther 305 680–687 Occurrence Handle12606677 Occurrence Handle10.1124/jpet.102.046359 Occurrence Handle1:CAS:528:DC%2BD3sXjt12mu7s%3D

    Article  PubMed  CAS  Google Scholar 

  • R Takahata B Moghaddam (2003) ArticleTitleActivation of glutamate neurotransmission in the prefrontal cortex sustains the motoric and dopaminergic effects of phencyclidine Neuropsychopharmacology 28 1117–1124 Occurrence Handle12700703 Occurrence Handle1:CAS:528:DC%2BD3sXjvF2ltb4%3D

    PubMed  CAS  Google Scholar 

  • CA Tamminga A Carlsson (2002) ArticleTitlePartial dopamine agonists and dopaminergic stabilizers, in the treatment of psychosis Curr Drug Target CNS Neurol Disord 1 141–147 Occurrence Handle10.2174/1568007024606195 Occurrence Handle1:CAS:528:DC%2BD38XjvV2nurc%3D

    Article  CAS  Google Scholar 

  • CA Tamminga MH Schaffer RC Smith JM Davis (1978) ArticleTitleSchizophrenic symptoms improve with apomorphine Science 200 567–568 Occurrence Handle347574 Occurrence Handle10.1126/science.347574 Occurrence Handle1:STN:280:DyaE1c7lvFOjsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • TM Tzschentke (2001) ArticleTitlePharmacology and behavioral pharmacology of the mesocortical dopamine system Prog Neurobiol 63 241–320 Occurrence Handle11115727 Occurrence Handle10.1016/S0301-0082(00)00033-2 Occurrence Handle1:CAS:528:DC%2BD3cXoslCks7o%3D

    Article  PubMed  CAS  Google Scholar 

  • P Vezina G Blanc J Glowinski J-P Tassin (1991) ArticleTitleOpposed behavioural outputs of increased dopamine transmission in prefrontocortical and subcortical areas: a role for the cortical D1 dopamine receptor Eur J Neurosci 3 1001–1007 Occurrence Handle12106258 Occurrence Handle10.1111/j.1460-9568.1991.tb00036.x

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Del Arco, A., Mora, F., Mohammed, A. et al. Stimulation of D2 receptors in the prefrontal cortex reduces PCP-induced hyperactivity, acetylcholine release and dopamine metabolism in the nucleus accumbens. J Neural Transm 114, 185–193 (2007). https://doi.org/10.1007/s00702-006-0533-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-006-0533-3

Navigation