Skip to main content

Advertisement

SpringerLink
Log in

Alterations in prefrontal glutamatergic and noradrenergic systems following MK-801 administration in rats prenatally exposed to methylazoxymethanol at gestational day 17

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

Abstract

Rationale

Prenatal methylazoxymethanol (MAM) administration at gestational day 17 has been shown to induce in adult rats schizophrenia-like behaviours as well as morphological and/or functional abnormalities in structures such as the hippocampus, medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc), consistent with human data.

Objectives

The aim of the present study was to further characterize the neurochemical alterations associated with this neurodevelopmental animal model of schizophrenia.

Materials and methods

We performed simultaneous measurements of locomotor activity and extracellular concentrations of glutamate, dopamine and noradrenaline in the mPFC and the NAcc of adult rats prenatally exposed to MAM or saline after acute systemic injection of a noncompetitive NMDA antagonist, MK-801 (0.1 mg/kg s.c.).

Results

A significant attenuation of the MK-801-induced increase in glutamate levels associated with a potentiation of the increase in noradrenaline concentrations was found in the mPFC of MAM-exposed rats, whereas no significant change was observed in the NAcc. MAM-exposed rats also exhibited an exaggerated locomotor hyperactivity, in line with the exacerbation of symptoms reported in schizophrenic patients after administration of noncompetitive NMDA antagonists.

Conclusions

Given the importance of the mPFC in regulating the hyperlocomotor effect of NMDA antagonists, our results suggest that the prefrontal neurochemical alterations induced by MK-801 may sustain the exaggerated locomotor response in MAM-exposed rats.

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
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M, van Dyck CH, Charney DS, Innis RB, Laruelle M (1998) Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 155:761–767

    PubMed  CAS  Google Scholar 

  • Adams B, Moghaddam B (1998) Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine. J Neurosci 18:5545–5554

    PubMed  CAS  Google Scholar 

  • Akbarian S, Sucher NJ, Bradley D, Tafazzoli A, Trinh D, Hetrick WP, Potkin SG, Sandman CA, Bunney WE, Jones EG (1996) Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J Neurosci 16:19–30

    PubMed  CAS  Google Scholar 

  • Al-Amin HA, Weinberger DR, Lipska BK (2000) Exaggerated MK-801-induced motor hyperactivity in rats with the neonatal lesion of the ventral hippocampus. Behav Pharmacol 11:269–278

    PubMed  CAS  Google Scholar 

  • Al-Amin HA, Weickert CS, Weinberger DR, Lipska BK (2001) Delayed onset of enhanced MK-801-induced motor hyperactivity after neonatal lesions of the rat ventral hippocampus. Biol Psychiatry 49:528–539

    Article  PubMed  CAS  Google Scholar 

  • Baldessarini RJ, Huston-Lyons D, Campbell A, Marsh E, Cohen BM (1992) Do central antiadrenergic actions contribute to the atypical properties of clozapine? Br J Psychiatry 17:12–16

    Google Scholar 

  • Benes FM (1993) The relationship between structural brain imaging and histopathologic findings in schizophrenia research. Harv Rev Psychiatry 1:100–109

    PubMed  CAS  Google Scholar 

  • Berridge CW, Stratford TL, Foote SL, Kelley AE (1997) Distribution of dopamine beta-hydroxylase-like immunoreactive fibers within the shell subregion of the nucleus accumbens. Synapse 27:230–241

    Article  PubMed  CAS  Google Scholar 

  • Bert L, Robert F, Denoroy L, Stoppini L, Renaud B (1996) Enhanced temporal resolution for the microdialysis monitoring of catecholamines and excitatory amino acids using capillary electrophoresis with laser-induced fluorescence detection. Analytical developments and in vitro validations. J Chromatogr A 755:99–111

    Article  PubMed  CAS  Google Scholar 

  • Bogerts B, Meertz E, Schonfeldt-Bausch R (1985) Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage. Arch Gen Psychiatry 42:784–791

    PubMed  CAS  Google Scholar 

  • Borrell J, Vela JM, Arevalo-Martin A, Molina-Holgado E, Guaza C (2002) Prenatal immune challenge disrupts sensorimotor gating in adult rats. Implications for the etiopathogenesis of schizophrenia. Neuropsychopharmacology 26:204–215

    Article  PubMed  CAS  Google Scholar 

  • Breier A, Su TP, Saunders R et al (1997) Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci USA 94:2569–2574

    Article  PubMed  CAS  Google Scholar 

  • Bruton CJ, Crow TJ, Frith CD, Johnstone EC, Owens DG, Roberts GW (1990) Schizophrenia and the brain: a prospective clinico-neuropathological study. Psychol Med 20:285–304

    Article  PubMed  CAS  Google Scholar 

  • Cannon M, Jones PB, Murray RM (2002) Obstetric complications and schizophrenia: historical and meta-analytic review. Am J Psychiatry 159:1080–1092

    Article  PubMed  Google Scholar 

  • Csernansky JG, Joshi S, Wang L, Haller JW, Gado M, Miller JP, Grenander U, Miller MI (1998) Hippocampal morphometry in schizophrenia by high dimensional brain mapping. Proc Natl Acad Sci USA 95:11406–11411

    Article  PubMed  CAS  Google Scholar 

  • Druhan JP, Rajabi H, Stewart J (1996) MK-801 increases locomotor activity without elevating extracellular dopamine levels in the nucleus accumbens. Synapse 24:135–146

    Article  PubMed  CAS  Google Scholar 

  • Falkai P, Bogerts B, Rozumek M (1988) Limbic pathology in schizophrenia: the entorhinal region—a morphometric study. Biol Psychiatry 24:515–521

    Article  PubMed  CAS  Google Scholar 

  • Faustman WO, Bardgett M, Faull KF, Pfefferbaum A, Csernansky JG (1999) Cerebrospinal fluid glutamate inversely correlates with positive symptom severity in unmedicated male schizophrenic/schizoaffective patients. Biol Psychiatry 45:68–75

    Article  PubMed  CAS  Google Scholar 

  • Flagstad P, Mork A, Glenthoj BY, van Beek J, Michael-Titus AT, Didriksen M (2004) Disruption of neurogenesis on gestational day 17 in the rat causes behavioral changes relevant to positive and negative schizophrenia symptoms and alters amphetamine-induced dopamine release in nucleus accumbens. Neuropsychopharmacology 29:2052–2064

    Article  PubMed  CAS  Google Scholar 

  • Flagstad P, Glenthoj BY, Didriksen M (2005) Cognitive deficits caused by late gestational disruption of neurogenesis in rats: a preclinical model of schizophrenia. Neuropsychopharmacology 30:250–260

    Article  PubMed  Google Scholar 

  • Fortier ME, Joober R, Luheshi GN, Boksa P (2004) Maternal exposure to bacterial endotoxin during pregnancy enhances amphetamine-induced locomotion and startle responses in adult rat offspring. J Psychiatr Res 38:335–345

    Article  PubMed  Google Scholar 

  • Geddes JR, Lawrie SM (1995) Obstetric complications and schizophrenia: a meta-analysis. Br J Psychiatry 167:786–793

    Article  PubMed  CAS  Google Scholar 

  • Glantz LA, Lewis DA (2000) Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 57:65–73

    Article  PubMed  CAS  Google Scholar 

  • Gourevitch R, Rocher C, Le Pen G, Krebs MO, Jay TM (2004) Working memory deficits in adult rats after prenatal disruption of neurogenesis. Behav Pharmacol 15:287–292

    Article  PubMed  CAS  Google Scholar 

  • Harkin A, Morris K, Kelly JP, O’Donnell JM, Leonard BE (2001) Modulation of MK-801-induced behaviour by noradrenergic agents in mice. Psychopharmacology 154:177–188

    Article  PubMed  CAS  Google Scholar 

  • Harrison PJ, Weinberger DR (2005) Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10:40–68

    Article  PubMed  CAS  Google Scholar 

  • Heckers S, Rauch SL, Goff D, Savage CR, Schacter DL, Fischman AJ, Alpert NM (1998) Impaired recruitment of the hippocampus during conscious recollection in schizophrenia. Nat Neurosci 1:318–323

    Article  PubMed  CAS  Google Scholar 

  • Ito K, Abekawa T, Koyama T (2006) Relationship between development of cross-sensitization to MK-801 and delayed increases in glutamate levels in the nucleus accumbens induced by a high dose of methamphetamine. Psychopharmacology 187:293–302

    Article  PubMed  CAS  Google Scholar 

  • Jentsch JD, Tran A, Taylor JR, Roth RH (1998) Prefrontal cortical involvement in phencyclidine-induced activation of the mesolimbic dopamine system: behavioral and neurochemical evidence. Psychopharmacology 138:89–95

    Article  PubMed  CAS  Google Scholar 

  • Kato K, Shishido T, Ono M, Shishido K, Kobayashi M, Suzuki H, Nabeshima T, Furukawa H, Niwa S (2000) Effects of phencyclidine on behavior and extracellular levels of dopamine and its metabolites in neonatal ventral hippocampal damaged rats. Psychopharmacology 150:163–169

    Article  PubMed  CAS  Google Scholar 

  • Kemali D, Maj M, Galderisi S, Grazia Ariano M, Starace F (1990) Factors associated with increased noradrenaline levels in schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry 14:49–59

    Article  PubMed  CAS  Google Scholar 

  • Kristiansen LV, Huerta I, Beneyto M, Meador-Woodruff JH (2006) NMDA receptors and schizophrenia. Curr Opin Pharmacol (in press)

  • Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB, Charney DS (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 51:199–214

    PubMed  CAS  Google Scholar 

  • Krystal JH, D’Souza DC, Mathalon D, Perry E, Belger A, Hoffman R (2003) NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development. Psychopharmacology 169:215–233

    Article  PubMed  CAS  Google Scholar 

  • Lahti AC, Koffel B, LaPorte D, Tamminga CA (1995) Subanesthetic doses of ketamine stimulate psychosis in schizophrenia. Neuropsychopharmacology 13:9–19

    Article  PubMed  CAS  Google Scholar 

  • Lake CR, Sternberg DE, van Kammen DP, Ballenger JC, Ziegler MG, Post RM, Kopin IJ, Bunney WE (1980) Schizophrenia: elevated cerebrospinal fluid norepinephrine. Science 207:331–333

    Article  PubMed  CAS  Google Scholar 

  • Laruelle M, Abi-Dargham A, van Dyck CH et al (1996) Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci USA 93:9235–9240

    Article  PubMed  CAS  Google Scholar 

  • Laruelle M, Kegeles LS, Abi-Dargham A (2003) Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Ann NY Acad Sci 1003:138–158

    Article  PubMed  CAS  Google Scholar 

  • Lavin A, Moore HM, Grace AA (2005) Prenatal disruption of neocortical development alters prefrontal cortical neuron responses to dopamine in adult rats. Neuropsychopharmacology 30:1426–1435

    Article  PubMed  CAS  Google Scholar 

  • Le Pen G, Gourevitch R, Hazane F, Hoareau C, Jay TM, Krebs MO (2006) Peri-pubertal maturation after developmental disturbance: a model for psychosis onset in the rat. Neuroscience 143:395–405

    Article  PubMed  CAS  Google Scholar 

  • Lipska BK (2004) Using animal models to test a neurodevelopmental hypothesis of schizophrenia. J Psychiatry Neurosci 29:282–286

    PubMed  Google Scholar 

  • Lipska BK, Jaskiw GE, Weinberger DR (1993) Postpubertal emergence of hyperresponsiveness to stress and to amphetamine after neonatal excitotoxic hippocampal damage: a potential animal model of schizophrenia. Neuropsychopharmacology 9:67–75

    PubMed  CAS  Google Scholar 

  • Lorrain DS, Baccei CS, Bristow LJ, Anderson JJ, Varney MA (2003a) Effects of ketamine and N-methyl-d-aspartate on glutamate and dopamine release in rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 117:697–706

    Article  PubMed  CAS  Google Scholar 

  • Lorrain DS, Schaffhauser H, Campbell UC, Baccei CS, Correa LD, Rowe B, Rodriguez DE, Anderson JJ, Varney MA, Pinkerton AB, Vernier JM, Bristow LJ (2003b) Group II mGlu receptor activation suppresses norepinephrine release in the ventral hippocampus and locomotor responses to acute ketamine challenge. Neuropsychopharmacology 28:1622–1632

    Article  PubMed  CAS  Google Scholar 

  • Loscher W, Honack D (1992) The behavioural effects of MK-801 in rats: involvement of dopaminergic, serotonergic and noradrenergic systems. Eur J Pharmacol 215:199–208

    Article  PubMed  CAS  Google Scholar 

  • Luby ED, Cohen BD, Rosenbaum G, Gottlieb JS, Kelley R (1959) Study of a new schizophrenomimetic drug; sernyl. Arch Neurol Psychiatry 81:363–369

    CAS  Google Scholar 

  • Malhotra AK, Pinals DA, Adler CM, Elman I, Clifton A, Pickar D, Breier A (1997) Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsychopharmacology 17:141–150

    Article  PubMed  CAS  Google Scholar 

  • Marenco S, Weinberger DR (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 

  • Mathe JM, Nomikos GG, Hildebrand BE, Hertel P, Svensson TH (1996) Prazosin inhibits MK-801-induced hyperlocomotion and dopamine release in the nucleus accumbens. Eur J Pharmacol 309:1–11

    Article  PubMed  CAS  Google Scholar 

  • Mathe JM, Nomikos GG, Schilstrom B, Svensson TH (1998) Non-NMDA excitatory amino acid receptors in the ventral tegmental area mediate systemic dizocilpine (MK-801) induced hyperlocomotion and dopamine release in the nucleus accumbens. J Neurosci Res 51:583–592

    Article  PubMed  CAS  Google Scholar 

  • Mathe JM, Nomikos GG, Blakeman KH, Svensson TH (1999) Differential actions of dizocilpine (MK-801) on the mesolimbic and mesocortical dopamine systems: role of neuronal activity. Neuropharmacology 38:121–128

    Article  PubMed  CAS  Google Scholar 

  • Mednick SA, Machon RA, Huttunen MO, Bonett D (1988) Adult schizophrenia following prenatal exposure to an influenza epidemic. Arch Gen Psychiatry 45:189–192

    PubMed  CAS  Google Scholar 

  • Moghaddam B, Adams B, Verma A, Daly D (1997) Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci 17:2921–2927

    PubMed  CAS  Google Scholar 

  • Moore H, Jentsch JD, Ghajarnia M, Geyer MA, Grace AA (2006) A neurobehavioral systems analysis of adult rats exposed to methylazoxymethanol acetate on E17: implications for the neuropathology of schizophrenia. Biol Psychiatry 60:253–264

    Article  PubMed  CAS  Google Scholar 

  • O’Callaghan E, Sham P, Takei N, Glover G, Murray RM (1991) Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic. Lancet 337:1248–1250

    Article  PubMed  CAS  Google Scholar 

  • Ouagazzal A, Nieoullon A, Amalric M (1993) Effects of dopamine D1 and D2 receptor blockade on MK-801-induced hyperlocomotion in rats. Psychopharmacology 111:427–434

    Google Scholar 

  • Ozawa K, Hashimoto K, Kishimoto T, Shimizu E, Ishikura H, Iyo M (2006) Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia. Biol Psychiatry 59:546–554

    Article  PubMed  CAS  Google Scholar 

  • Parsons LH, Justice JB (1992) Extracellular concentration and in vivo recovery of dopamine in the nucleus accumbens using microdialysis. J Neurochem 58:212–218

    Article  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic, San Diego

    Google Scholar 

  • Penschuck S, Flagstad P, Didriksen M, Leist M, Michael-Titus AT (2006) Decrease in parvalbumin-expressing neurons in the hippocampus and increased phencyclidine-induced locomotor activity in the rat methylazoxymethanol (MAM) model of schizophrenia. Eur J Neurosci 23:279–284

    Article  PubMed  Google Scholar 

  • Pilowsky LS, Bressan RA, Stone JM, Erlandsson K, Mulligan RS, Krystal JH, Ell PJ (2006) First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients. Mol Psychiatry 11:118–119

    Article  PubMed  CAS  Google Scholar 

  • Rapoport JL, Addington AM, Frangou S, Psych MR (2005) The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry 10:434–449

    Article  PubMed  CAS  Google Scholar 

  • Roberts GW, Colter N, Lofthouse R, Johnstone EC, Crow TJ (1987) Is there gliosis in schizophrenia? Investigation of the temporal lobe. Biol Psychiatry 22:1459–1468

    Article  PubMed  CAS  Google Scholar 

  • Sams-Dodd F (1996) Phencyclidine-induced stereotyped behaviour and social isolation in rats: a possible animal model of schizophrenia. Behav Pharmacol 7:3–23

    PubMed  CAS  Google Scholar 

  • Sams-Dodd F, Lipska BK, Weinberger DR (1997) Neonatal lesions of the rat ventral hippocampus result in hyperlocomotion and deficits in social behaviour in adulthood. Psychopharmacology 132:303–310

    Article  PubMed  CAS  Google Scholar 

  • Shi L, Fatemi SH, Sidwell RW, Patterson PH (2003) Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci 23:297–302

    PubMed  Google Scholar 

  • Svensson TH (2000) Dysfunctional brain dopamine systems induced by psychotomimetic NMDA-receptor antagonists and the effects of antipsychotic drugs. Brain Res Brain Res Rev 31:320–329

    Article  PubMed  CAS  Google Scholar 

  • Swanson CJ, Schoepp DD (2003) A role for noradrenergic transmission in the actions of phencyclidine and the antipsychotic and antistress effects of mGlu2/3 receptor agonists. Ann NY Acad Sci 1003:309–317

    Article  PubMed  CAS  Google Scholar 

  • Takahata R, Moghaddam B (2003) Activation of glutamate neurotransmission in the prefrontal cortex sustains the motoric and dopaminergic effects of phencyclidine. Neuropsychopharmacology 28:1117–1124

    PubMed  CAS  Google Scholar 

  • Tsai G, Passani LA, Slusher BS, Carter R, Baer L, Kleinman JE, Coyle JT (1995) Abnormal excitatory neurotransmitter metabolism in schizophrenic brains. Arch Gen Psychiatry 52:829–836

    PubMed  CAS  Google Scholar 

  • Tzschentke TM, Schmidt WJ (1998) Discrete quinolinic acid lesions of the rat prelimbic medial prefrontal cortex affect cocaine- and MK-801-, but not morphine- and amphetamine-induced reward and psychomotor activation as measured with the place preference conditioning paradigm. Behav Brain Res 97:115–127

    Article  PubMed  CAS  Google Scholar 

  • van Kammen DP, Peters J, van Kammen WB, Nugent A, Goetz KL, Yao J, Linnoila M (1989) CSF norepinephrine in schizophrenia is elevated prior to relapse after haloperidol withdrawal. Biol Psychiatry 26:176–188

    Article  PubMed  Google Scholar 

  • Verma A, Moghaddam B (1996) NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by dopamine. J Neurosci 16:373–379

    PubMed  CAS  Google Scholar 

  • Wadenberg ML, Hertel P, Fernholm R, Hygge Blakeman K, Ahlenius S, Svensson TH (2000) Enhancement of antipsychotic-like effects by combined treatment with the alpha1-adrenoceptor antagonist prazosin and the dopamine D2 receptor antagonist raclopride in rats. J Neural Transm 107:1229–1238

    Article  PubMed  CAS  Google Scholar 

  • Wedzony K, Klimek V, Golembiowska K (1993) MK-801 elevates the extracellular concentration of dopamine in the rat prefrontal cortex and increases the density of striatal dopamine D1 receptors. Brain Res 622:325–329

    Article  PubMed  CAS  Google Scholar 

  • Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44:660–669

    PubMed  CAS  Google Scholar 

  • Weinberger DR, Berman KF, Zec RF (1986) Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. Arch Gen Psychiatry 43:114–124

    PubMed  CAS  Google Scholar 

  • Yamamoto K, Hornykiewicz O (2004) Proposal for a noradrenaline hypothesis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 28:913–922

    Article  PubMed  CAS  Google Scholar 

  • Yan QS, Reith ME, Jobe PC, Dailey JW (1997) Dizocilpine (MK-801) increases not only dopamine but also serotonin and norepinephrine transmissions in the nucleus accumbens as measured by microdialysis in freely moving rats. Brain Res 765:149–158

    Article  PubMed  CAS  Google Scholar 

  • Zahm DS, Brog JS (1992) On the significance of subterritories in the “accumbens” part of the rat ventral striatum. Neuroscience 50:751–767

    Article  PubMed  CAS  Google Scholar 

  • Zuckerman L, Weiner I (2005) Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring. J Psychiatr Res 39:311–323

    Article  PubMed  Google Scholar 

  • Zuckerman L, Rehavi M, Nachman R, Weiner I (2003) Immune activation during pregnancy in rats leads to a postpubertal emergence of disrupted latent inhibition, dopaminergic hyperfunction, and altered limbic morphology in the offspring: a novel neurodevelopmental model of schizophrenia. Neuropsychopharmacology 28:1778–1789

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM Equipe Avenir, JE 2441, Laboratoire de Neurobiologie et Psychopathologie, Université de Nice-Sophia Antipolis, Parc Valrose, 06108, Nice cedex 2, France

    Isabelle Léna, Aline Chessel & René Garcia

  2. INSERM U796, Physiopathologie des Maladies Psychiatriques, Université René Descartes, Hôpital Sainte-Anne, 75014, Paris, France

    Gwenaëlle Le Pen & Marie-Odile Krebs

Authors
  1. Isabelle Léna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aline Chessel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gwenaëlle Le Pen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marie-Odile Krebs
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. René Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isabelle Léna.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Léna, I., Chessel, A., Le Pen, G. et al. Alterations in prefrontal glutamatergic and noradrenergic systems following MK-801 administration in rats prenatally exposed to methylazoxymethanol at gestational day 17. Psychopharmacology 192, 373–383 (2007). https://doi.org/10.1007/s00213-007-0719-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-007-0719-x

Keywords

Search

Navigation