Skip to main content

Advertisement

SpringerLink
Log in

Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Perinatal phencyclidine (PCP) administration in rat blocks the N-methyl d-aspartate receptor (NMDAR) and causes symptoms reminiscent of schizophrenia in human. A growing body of evidence suggests that alterations in γ-aminobutyric acid (GABA) interneuron neurotransmission may be associated with schizophrenia. Neuregulin-1 (NRG-1) is a trophic factor important for neurodevelopment, synaptic plasticity, and wiring of GABA circuits.

Objectives

The aim of this study was to determine the long-term effects of perinatal PCP administration on the projection and local circuit neurons and NRG-1 expression in the cortex and hippocampus.

Methods

Rats were treated on postnatal day 2 (P2), P6, P9, and P12 with either PCP (10 mg/kg) or saline. Morphological studies and determination of NRG-1 expression were performed at P70.

Results

We demonstrate reduced densities of principal neurons in the CA3 and dentate gyrus (DG) subregions of the hippocampus and a reduction of major interneuronal populations in all cortical and hippocampal regions studied in PCP-treated rats compared with controls. For the first time, we show the reduced density of reelin- and somatostatin-positive cells in the cortex and hippocampus of animals perinatally treated with PCP. Furthermore, an increase in the numbers of perisomatic inhibitory terminals around the principal cells was observed in the motor cortex and DG. We also show that perinatal PCP administration leads to an increased NRG-1 expression in the cortex and hippocampus.

Conclusion

Taken together, our findings demonstrate that perinatal PCP administration increases NRG-1 expression and reduces the number of projecting and local circuit neurons, revealing complex consequences of NMDAR blockade.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

GABA:

γ-Aminobutyric acid

NRG-1:

Neuregulin-1

PCP:

Phencyclidine

DG:

Dentate gyrus

NMDA:

N-methyl-d-aspartate

NMDAR:

N-methyl-d-aspartate receptor

PV:

Parvalbumin

SST:

Somatostatin

CR:

Calretinin

VIP:

Vasointestinal peptide

PBS:

Phosphate-buffered saline

VGAT:

Vesicular GABA transporter

NeuN:

Neuron-specific nuclear antigen

CGCx:

Cingulate cortex

RSCx:

Retrosplenial cortex

MCX:

Motor cortex

References

  • Abdul-Monim Z, Neill JC, Reynolds GP (2007) Sub-chronic psychotomimetic phencyclidine induces deficits in reversal learning and alterations in parvalbumin-immunoreactive expression in the rat. J Psychopharmacol 21:198–205

    Article  PubMed  CAS  Google Scholar 

  • Abekawa T, Ito K, Nakagawa S, Koyama T (2007) Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats. Psychopharmacology 192:303–316

    Article  PubMed  CAS  Google Scholar 

  • Adams SM, de Rivero Vaccari JC, Corriveau RA (2004) Pronounced cell death in the absence of NMDA receptors in the developing somatosensory thalamus. J Neurosci 24:9441–9450

    Article  PubMed  CAS  Google Scholar 

  • Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE Jr, Jones EG (1995) Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry 52:258–266

    Article  PubMed  CAS  Google Scholar 

  • Amitai N, Kuczenski R, Behrens MM, Markou A (2012) Repeated phencyclidine administration alters glutamate release and decreases GABA markers in the prefrontal cortex of rats. Neuropharmacology 62:1422–1431

    Article  PubMed  CAS  Google Scholar 

  • Anastasio NC, Johnson KM (2008) Differential regulation of the NMDA receptor by acute and sub-chronic phencyclidine administration in the developing rat. J Neurochem 104:1210–1218

    Google Scholar 

  • Anastasio NC, Xia Y, O'Connor ZR, Johnson KM (2009) Differential role of N-methyl-d-aspartate receptor subunits 2A and 2B in mediating phencyclidine-induced perinatal neuronal apoptosis and behavioral deficits. Neuroscience 163:1181-1191

    Google Scholar 

  • Andersen JD, Pouzet B (2004) Spatial memory deficits induced by perinatal treatment of rats with PCP and reversal effect of d-serine. Neuropsychopharmacology 29:1080–1090

    Article  PubMed  CAS  Google Scholar 

  • Benes FM, McSparren J, Bird ED, SanGiovanni JP, Vincent SL (1991) Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. Arch Gen Psychiatry 48:996–1001

    Article  PubMed  CAS  Google Scholar 

  • Bird ED, Spokes EGS, Iversen LL (1979) Increased dopamine concentration in limbic areas of brain from patients dying with schizophrenia. Brain 102:347–360

    Article  PubMed  CAS  Google Scholar 

  • Cabungcal J-H, Nicolas D, Kraftsik R, Cuénod M, Do KQ, Hornung J-P (2006) Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons: relevance to schizophrenia. Neurobiol Dis 22:624–637

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Beffert U, Ertunc M, Tang T-S, Kavalali ET, Bezprozvanny I, Herz J (2005) Reelin modulates NMDA receptor activity in cortical neurons. J Neurosci 25:8209–8216

    Article  PubMed  CAS  Google Scholar 

  • Cochran SM, Fujimura M, Morris BJ, Pratt JA (2002) Acute and delayed effects of phencyclidine upon mRNA levels of markers of glutamatergic and GABAergic neurotransmitter function in the rat brain. Synapse 46:206–214

    Article  PubMed  CAS  Google Scholar 

  • Costa E, Davis J, Grayson DR, Guidotti A, Pappas GD, Pesold C (2001) Dendritic spine hypoplasticity and downregulation of reelin and GABAergic tone in schizophrenia vulnerability. Neurobiol Dis 8:723–742

    Article  PubMed  CAS  Google Scholar 

  • Coyle JT (2004) The GABA-glutamate connection in schizophrenia: which is the proximate cause? Biochem Pharmacol 68:1507–1514

    Article  PubMed  CAS  Google Scholar 

  • de Lecea L, del Río JA, Soriano E (1995) Developmental expression of parvalbumin mRNA in the cerebral cortex and hippocampus of the rat. Mol Brain Res 32:1–13

    Article  PubMed  Google Scholar 

  • Depoortere R, Dargazanli G, Estenne-Bouhtou G, Coste A, Lanneau C, Desvignes C, Poncelet M, Heaulme M, Santucci V, Decobert M, Cudennec A, Voltz C, Boulay D, Paul Terranova J, Stemmelin J, Roger P, Marabout B, Sevrin M, Vige X, Biton B, Steinberg R, Francon D, Alonso R, Avenet P, Oury-Donat F, Perrault G, Griebel G, George P, Soubrie P, Scatton B (2005) Neurochemical, electrophysiological and pharmacological profiles of the selective inhibitor of the glycine transporter-1 SSR504734, a potential new type of antipsychotic. Neuropsychopharmacology 30:1963–1985

    Article  PubMed  CAS  Google Scholar 

  • du Bois TM, Newell KA, Han M, Deng C, Huang X-F (2009) Perinatal PCP treatment alters the developmental expression of prefrontal and hippocampal muscarinic receptors. Progr Neuro-Psychopharmacol Biol Psychiatr 33:37–40

    Article  Google Scholar 

  • du Bois TM, Newell KA, Huang X-F (2012) Perinatal phencyclidine treatment alters neuregulin 1/erbB4 expression and activation in later life. Eur Neuropsychopharmacol 22:356–363

    Article  PubMed  Google Scholar 

  • Eastwood SL, Harrison PJ (2003) Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis. Mol Psychiatry 8(769):821–831

    Article  CAS  Google Scholar 

  • Eastwood SL, Harrison PJ (2006) Cellular basis of reduced cortical reelin expression in schizophrenia. Am J Psychiatry 163:540–542

    Article  PubMed  Google Scholar 

  • Fazzari P, Paternain AV, Valiente M, Pla R, Lujan R, Lloyd K, Lerma J, Marin O, Rico B (2010) Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling. Nature 464:1376–1380

    Article  PubMed  CAS  Google Scholar 

  • Feng Y, Wang X, Guo C, Yang Y, Li J, Su Y, Si T (2010) Expressions of neuregulin 1beta and ErbB4 in prefrontal cortex and hippocampus of a rat schizophrenia model induced by chronic MK-801 administration. J Biomed Biotechnol 2010:859516

  • Fisahn A, Jr N, Yan L, As B (2009) Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia. Cerebr Cortex 19:612–618

    Article  Google Scholar 

  • Fukushima F, Nakao K, Shinoe T, Fukaya M, Muramatsu S-i, Sakimura K, Kataoka H, Mori H, Watanabe M, Manabe T, Mishina M (2009) Ablation of NMDA Receptors Enhances the Excitability of Hippocampal CA3 Neurons. PLoS ONE 4: e3993.

  • Fung S, Webster M, Sivagnanasundaram S, Duncan C, Elashoff M, Weickert C (2010) Expression of interneuron markers in the dorsolateral prefrontal cortex of the developing human and in schizophrenia. Am J Pscychiatry 12:1479–1488

    Article  Google Scholar 

  • Garcia RAG, Vasudevan K, Buonanno A (2000) The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses. Proc Natl Acad Sci U S A 97:3596–3601

    Article  PubMed  CAS  Google Scholar 

  • Gelman DM, Marín O (2010) Generation of interneuron diversity in the mouse cerebral cortex. Eur J Neurosci 31:2136–2141

    Article  PubMed  Google Scholar 

  • Guidotti A, Auta J, Chen Y, Davis JM, Dong E, Gavin DP, Grayson DR, Matrisciano F, Pinna G, Satta R, Sharma RP, Tremolizzo L, Tueting P (2010) Epigenetic GABAergic targets in schizophrenia and bipolar disorder. Neuropharmacology 60:1007–1016

    Article  PubMed  Google Scholar 

  • Guidotti A, Auta J, Davis JM, Gerevini VD, Dwivedi Y, Grayson DR, Impagnatiello F, Pandey G, Pesold C, Sharma R, Uzunov D, Costa E (2000) Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry 57:1061–1069

    Article  PubMed  CAS  Google Scholar 

  • Harvey L, Boksa P (2012) A stereological comparison of GAD67 and reelin expression in the hippocampal stratum oriens of offspring from two mouse models of maternal inflammation during pregnancy. Neuropharmacology 62:1767–1776

    Article  PubMed  CAS  Google Scholar 

  • Heckers S, Stone D, Walsh J, Shick J, Koul P, Benes FM (2002) Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia. Arch Gen Psychiatry 59:521–529

    Article  PubMed  CAS  Google Scholar 

  • Howard C, Reed M (1998) Unbiased stereology. Three-dimensional measurement in microscopy. BIOS Scientific Publishers, Oxford

    Google Scholar 

  • Huang YZ, Won S, Ali DW, Wang Q, Tanowitz M, Du QS, Pelkey KA, Yang DJ, Xiong WC, Salter MW, Mei L (2000) Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses. Neuron 26:443–455

    Article  PubMed  CAS  Google Scholar 

  • Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vöckler J, Dikranian K, Tenkova T, Stefovska V, Turski L, Olney J (1999) Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283:70–74

    Article  PubMed  CAS  Google Scholar 

  • Impagnatiello F, Guidotti AR, Pesold C, Dwivedi Y, Caruncho H, Pisu MG, Uzunov DP, Smalheiser NR, Davis JM, Pandey GN, Pappas GD, Tueting P, Sharma RP, Costa E (1998) A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc Natl Acad Sci 95:15718–15723

    Article  PubMed  CAS  Google Scholar 

  • Irintchev A, Rollenhagen A, Troncoso E, Kiss JZ, Schachner M (2005) Structural and functional aberrations in the cerebral cortex of tenascin-C deficient mice. Cerebr Cortex 15:950–962

    Article  Google Scholar 

  • Jenkins TA, Harte MK, McKibben CE, Elliott JJ, Reynolds GP (2008) Disturbances in social interaction occur along with pathophysiological deficits following sub-chronic phencyclidine administration in the rat. Behav Brain Res 194:230–235

    Article  PubMed  CAS  Google Scholar 

  • Jenkins TA, Harte MK, Reynolds GP (2010) Effect of subchronic phencyclidine administration on sucrose preference and hippocampal parvalbumin immunoreactivity in the rat. Neurosci Lett 471:144–147

    Article  PubMed  CAS  Google Scholar 

  • Knuesel I (2010) Reelin-mediated signaling in neuropsychiatric and neurodegenerative diseases. Progr Neurobiol 91:257–274

    Article  CAS  Google Scholar 

  • Lee HJ, Jakovcevski I, Radonjic N, Hoelters L, Schachner M, Irintchev A (2009) Better functional outcome of compression spinal cord injury in mice is associated with enhanced H-reflex responses. Exp Neurol 216:365–374

    Article  PubMed  Google Scholar 

  • Lewis DA (2011) The chandelier neuron in schizophrenia. Dev Neurobiol 71:118–127

    Article  PubMed  CAS  Google Scholar 

  • Lewis DA, Gonzalez-Burgos G (2006) Pathophysiologically based treatment interventions in schizophrenia. Nat Med 12:1016–1022

    Article  PubMed  CAS  Google Scholar 

  • Liodis P, Denaxa M, Grigoriou M, Akufo-Addo C, Yanagawa Y, Pachnis V (2007) Lhx6 activity is required for the normal migration and specification of cortical interneuron subtypes. J Neurosci 27:3078–3089

    Article  PubMed  CAS  Google Scholar 

  • Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, Grace AA (2008) Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci 31:234–242

    Article  PubMed  CAS  Google Scholar 

  • Marenco S, Weinberger D (2000) The neurodevelopmental hypothesis of schizophrenia: following a trail of evidence from cradle to grave. Dev Psychopathol 12:501–527

    Article  PubMed  CAS  Google Scholar 

  • McKibben CE, Jenkins TA, Adams HN, Harte MK, Reynolds GP (2010) Effect of pretreatment with risperidone on phencyclidine-induced disruptions in object recognition memory and prefrontal cortex parvalbumin immunoreactivity in the rat. Behav Brain Res 208:132–136

    Article  PubMed  CAS  Google Scholar 

  • Mei L, Xiong W-C (2008) Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci 9:437–452

    Article  PubMed  CAS  Google Scholar 

  • Meyer G, Goffinet AM (1998) Prenatal development of reelin-immunoreactive neurons in the human neocortex. J Comp Neurol 397:29–40

    Article  PubMed  CAS  Google Scholar 

  • Meyer U, Nyffeler M, Engler A, Urwyler A, Schedlowski M, Knuesel I, Yee B, Feldon J (2006) The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. J Neurosci 26:4752–4762

    Article  PubMed  CAS  Google Scholar 

  • Morellini F, Sivukhina E, Stoenica L, Oulianova E, Bukalo O, Jakovcevski I, Dityatev A, Irintchev A, Schachner M (2010) Improved reversal learning and working memory and enhanced reactivity to novelty in mice with enhanced GABAergic innervation in the dentate gyrus. Cerebr Cortex 20:2712–2727

    Article  Google Scholar 

  • Mouri A, Noda Y, Enomoto T, Nabeshima T (2007) Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. Neurochem Int 51:173–184

    Article  PubMed  CAS  Google Scholar 

  • Nabeshima T, Yamaguchi K, Yamada K, Hiramatsu M, Kuwabara Y, Furukawa H, Kameyama T (1984) Sex-dependent differences in the pharmacological actions and pharmacokinetics of phencyclidine in rats. Eur J Pharmacol 97:217–227

    Google Scholar 

  • Nakatani-Pawlak A, Yamaguchi K, Tatsumi Y, Mizoguchi H, Yoneda Y (2009) Neonatal phencyclidine treatment in mice induces behavioral, histological and neurochemical abnormalities in adulthood. Biol Pharm Bull 32:1576–1583

    Article  PubMed  CAS  Google Scholar 

  • Nikonenko AG, Sun M, Lepsveridze E, Apostolova I, Petrova I, Irintchev A, Dityatev A, Schachner M (2006) Enhanced perisomatic inhibition and impaired long-term potentiation in the CA1 region of juvenile CHL1-deficient mice. Eur J Neurosci 23:1839–1852

    Article  PubMed  Google Scholar 

  • Okamoto M, Katayama T, Suzuki Y, Hoshino KY, Yamada H, Matsuoka N, Jodo E (2012) Neonatal administration of phencyclidine decreases the number of putative inhibitory interneurons and increases neural excitability to auditory paired clicks in the hippocampal CA3 region of freely moving adult mice. Neuroscience 224:268–281

    Article  PubMed  CAS  Google Scholar 

  • Olney J, Labruyere J, Wang G, Wozniak D, Price M, Sesma M (1991) NMDA antagonist neurotoxicity: mechanism and prevention. Science 254:1515–1518

    Google Scholar 

  • Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates. Academic, San Diego

    Google Scholar 

  • Perry T, Kish S, Buchanan J, Hansen S (1979) Gamma-aminobutyric-acid deficiency in brain of schizophrenic patients. Lancet 1:237–239

    Article  PubMed  CAS  Google Scholar 

  • Petronijevic N, Nikolic T, Radonjic N, Vilimanovich U, Trajkovic V, Bumbasirevic V (2010) Decreased neuregulin-1 in the cortex of rat pups as immediate effect of perinatal phencyclidine treatment. Eur Neuropsychopharmacol 20:S271–S272

    Article  Google Scholar 

  • Powell SB, Sejnowski TJ, Behrens MM (2012) Behavioral and neurochemical consequences of cortical oxidative stress on parvalbumin-interneuron maturation in rodent models of schizophrenia. Neuropharmacology 62:1322–1331

    Article  PubMed  CAS  Google Scholar 

  • Pratt JA, Winchester C, Egerton A, Cochran SM, Morris BJ (2008) Modelling prefrontal cortex deficits in schizophrenia: implications for treatment. Br J Pharmacol 153:S465–S470

    Article  PubMed  CAS  Google Scholar 

  • Radonjić NV, Knezević ID, Vilimanovich U, Kravic-Stevović T, Marina LV, Nikolić T, Todorović V, Bumbaširević V, Petronijević ND (2010) Decreased glutathione levels and altered antioxidant defense in an animal model of schizophrenia: long-term effects of perinatal phencyclidine administration. Neuropharmacology 58:739–745

    Article  PubMed  Google Scholar 

  • Radonjić NV, Petronijević ND, Vučković SM, Prostran MS, Nešic ZI, Todorović VR, Paunović VR (2008) Baseline temperature in an animal model of schizophrenia: long-term effects of perinatal phencyclidine administration. Physiol Behav 93:437–443

    Article  PubMed  Google Scholar 

  • Shelnutt SR, Gunnell M, Owens SM (1999) Sexual dimorphism in phencyclidine in vitro metabolism and pharmacokinetics in rats. J Pharmacol Exp Ther 290:1292-1298

    Google Scholar 

  • Sherman A, Davidson A, Baruah S, Hegwood T, Waziri R (1991) Evidence of glutamatergic deficiency in schizophrenia. Neurosci Lett 121:77–80

    Article  PubMed  CAS  Google Scholar 

  • Simpson M, Slater P, Deakin J, Royston M, Skan W (1989) Reduced GABA uptake sites in the temporal lobe in schizophrenia. Neurosci Lett 107:211–215

    Article  PubMed  CAS  Google Scholar 

  • Sircar R (2003) Postnatal phencyclidine-induced deficit in adult water maze performance is associated with N-methyl-d-aspartate receptor upregulation. Int J Dev Neurosci 21:159–167

    Article  PubMed  CAS  Google Scholar 

  • Stefansson H, Petursson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, Brynjolfsson J, Gunnarsdottir S, Ivarsson O, Chou TT, Hjaltason O, Birgisdottir B, Jonsson H, Gudnadottir VG, Gudmundsdottir E, Bjornsson A, Ingvarsson B, Ingason A, Sigfusson S, Hardardottir H, Harvey RP, Lai D, Zhou M, Brunner D, Mutel V, Gonzalo A, Lemke G, Sainz J, Johannesson G, Andresson T, Gudbjartsson D, Manolescu A, Frigge ML, Gurney ME, Kong A, Gulcher JR, Stefansson K (2002) Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 71:877–892

    Article  PubMed  Google Scholar 

  • Steullet P, Cabungcal J-H, Kulak A, Kraftsik R, Chen Y, Dalton TP, Cuenod M, Do KQ (2010) Redox dysregulation affects the ventral but not dorsal hippocampus: impairment of parvalbumin neurons, gamma oscillations, and related behaviors. J Neurosci 30:2547–2558

    Article  PubMed  CAS  Google Scholar 

  • Stojković T, Radonjić NV, Velimirović M, Jevtić G, Popović V, Doknić M, Petronijević ND (2012) Risperidone reverses phencyclidine induced decrease in glutathione levels and alterations of antioxidant defense in rat brain. Progr Neuro-Psychopharmacol Biol Psychiatr 39:192–199

    Google Scholar 

  • Tanaka DH, Maekawa K, Yanagawa Y, Obata K, Murakami F (2006) Multidirectional and multizonal tangential migration of GABAergic interneurons in the developing cerebral cortex. Development 133:2167–2176

    Article  PubMed  CAS  Google Scholar 

  • Thomsen MS, Christensen DZ, Hansen HH, Redrobe JP, Mikkelsen JD (2009) [alpha]7 Nicotinic acetylcholine receptor activation prevents behavioral and molecular changes induced by repeated phencyclidine treatment. Neuropharmacology 56:1001–1009

    Article  PubMed  CAS  Google Scholar 

  • Thomsen MS, Hansen HH, Mikkelsen JD (2010a) [alpha]7 Nicotinic receptor agonism mitigates phencyclidine-induced changes in synaptophysin and Arc gene expression in the mouse prefrontal cortex. Neurochem Int 57:756–761

    Article  PubMed  CAS  Google Scholar 

  • Thomsen MS, Hansen HH, Mikkelsen JD (2010b) Opposite effect of phencyclidine on activity-regulated cytoskeleton-associated protein (Arc) in juvenile and adult limbic rat brain regions. Neurochem Int 56:270–275

    Article  PubMed  CAS  Google Scholar 

  • Volk DW, Austin MC, Pierri JN, Sampson AR, Lewis DA (2000) Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical {gamma}-aminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatry 57:237–245

    Article  PubMed  CAS  Google Scholar 

  • Wang C, McInnis J, Ross-Sanchez M, Shinnick-Gallagher P, Wiley JL, Johnson KM (2001) Long-term behavioral and neurodegenerative effects of perinatal phencyclidine administration: implications for schizophrenia. Neuroscience 107:535–550

    Article  PubMed  CAS  Google Scholar 

  • Wang C, McInnis J, West JB, Bao J, Anastasio N, Guidry JA, Ye Y, Salvemini D, Johnson KM (2003) Blockade of phencyclidine-induced cortical apoptosis and deficits in prepulse inhibition by M40403, a superoxide dismutase mimetic. J Pharmacol Exp Ther 304:266–271

    Article  PubMed  CAS  Google Scholar 

  • Wang CZ, Yang SF, Xia Y, Johnson KM (2008) Postnatal phencyclidine administration selectively reduces adult cortical parvalbumin-containing interneurons. Neuropsychopharmacology 33:2442–2455

    Article  PubMed  CAS  Google Scholar 

  • Wessinger WD (1995) Sexual dimorphic effects of chronic phencyclidine in rats. Eur J Pharmacol 277:107–112

    Google Scholar 

  • Wiley JL, Bühler KG, Lavecchia KL, Johnson KM (2003) Pharmacological challenge reveals long-term effects of perinatal phencyclidine on delayed spatial alternation in rats. Progr Neuro-Psychopharmacol Biol Psychiatr 27:867–873

    Article  CAS  Google Scholar 

  • Woo T-U, Whitehead RE, Melchitzky DS, Lewis DA (1998) A subclass of prefrontal γ-aminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci U S A 95:5341–5346

    Article  PubMed  CAS  Google Scholar 

  • Zhang Z, Sun Q-Q (2011) Development of NMDA NR2 subunits and their roles in critical period maturation of neocortical GABAergic interneurons. Dev Neurobiol 71:221–245

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This study was supported by grant no. 175058 from the Ministry of Education, Science and Technological Development of the Republic of Serbia. N.R. was supported by Deutscher Akademischer Austausch Dienst (DAAD) Special Southeast Europe Program. We are grateful to Profs. Melitta Schachner and Hans Joachim Seitz from the University Medical Center Hamburg-Eppendorf for hospitality and support.

Conflicts of interest

All authors state no potential conflict of interest.

Author information

Authors and Affiliations

  1. Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Pasterova 2, 11000, Belgrade, Serbia

    Nevena V. Radonjić & Nataša D. Petronijević

  2. Zentrum für Molekulare Neurobiologie, University Hospital Hamburg-Eppendorf, Martinistrasse 52, Hamburg, Germany

    Igor Jakovcevski

  3. Institute of Histology and Embriology, School of Medicine, University of Belgrade, Višegradska 26, Belgrade, Serbia

    Vladimir Bumbaširević

Authors
  1. Nevena V. Radonjić
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Igor Jakovcevski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vladimir Bumbaširević
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nataša D. Petronijević
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nevena V. Radonjić.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Radonjić, N.V., Jakovcevski, I., Bumbaširević, V. et al. Perinatal phencyclidine administration decreases the density of cortical interneurons and increases the expression of neuregulin-1. Psychopharmacology 227, 673–683 (2013). https://doi.org/10.1007/s00213-013-2999-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-013-2999-7

Keywords

Search

Navigation