Skip to main content
SpringerLink
Log in

Phencyclidine-induced increases in striatal neuron firing in behaving rats: reversal by haloperidol and clozapine

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

Amphetamine and related drugs of abuse facilitate dopamine transmission in the striatum. This action is believed to underlie the increase in firing of striatal motor-related neurons after amphetamine administration in behaving rats. The present study extended this electrophysiological investigation to phencyclidine (PCP), a nonamphetamine psychomotor stimulant that acts primarily as a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) glutamate receptors. Like amphetamine, PCP (1.0, 2.5, or 5.0 mg/kg) increased the activity of striatal motor-related neurons concomitant with behavioral activation. These effects were blocked by subsequent administration of either 1.0 mg/kg haloperidol or 20.0 mg/kg clozapine, typical and atypical neuroleptics, respectively. Dizocilpine (MK-801), another noncompetitive NMDA antagonist, mimicked the effect of PCP. Collectively, these results indicate that amphetamine and NMDA antagonists exert comparable effects on striatal motor-related neurons, suggesting that the response of these cells to psychomotor stimulants is regulated by a dopaminergic-glutamatergic influence.

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

  • Angrist B (1987) Pharmacological models of schizophrenia. In: Henn FA, Delisi LE (eds) Handbook of schizophrenia, vol 2. Neurochemistry and neuropharmacology of schizophrenia. Elsevier, Amsterdam, pp 391–424

    Google Scholar 

  • Balster RL (1987) The behavioral pharmacology of phencylidine. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 1573–1579

    Google Scholar 

  • Butcher SP, Fairbrother IS, Kelly JS, Arbuthnott GW (1988) Amphetamine-induced dopamine release in the rat striatum: an in vivo microdialysis study. J Neurochem 50: 346–355

    PubMed  Google Scholar 

  • Carboni E, Imperato E, Perezzani L, Di Chiarra G (1989) Amphetamine, cocaine, phencyclidine and nomifensine increase extracellular dopamine comcentrations preferentially in the nucleus accumbens of freely moving rats. Neuroscience 2: 653–661

    Google Scholar 

  • Carelli RM, West MO (1991) Representation of the body by single neurons in the dorsolateral striatum of the awake, unrestrained rat. J Comp Neurol 309: 231–249

    PubMed  Google Scholar 

  • Carlsson A (1978) Antipsychotic drugs, neurotransmitters, and schizophrenia. Am J Psychiatry 135: 164–173

    Google Scholar 

  • Carter CJ, L'Heureux R, Scatton B (1988) Differential control by N-methyl-D-aspartate and kainate of striatal dopamine release in vivo: a trans-striatal dialysis study. J Neurochem 51: 462–468

    PubMed  Google Scholar 

  • Castellani S, Adams PM (1981) Effects of dopaminergic drugs on phencyclidine-induced behavior in the rat. Neuropharmacology 20: 371–374

    PubMed  Google Scholar 

  • Creese I, Iversen SD (1975) The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res 83: 419–436

    PubMed  Google Scholar 

  • Domino EF, Luby ED (1981) Abnormal mental states induced by phencyclidine as a model of schizophrenia. In: Domino EF (ed) PCP (phencyclidine): historical and current perspectives. NPP Books, Ann Arbor Mi, pp 400–418

    Google Scholar 

  • Dunnett SB, Robbins TW (1992) The functional role of mesotelencephalic dopamine systems. Biol Rev 67: 491–518

    PubMed  Google Scholar 

  • Ellenbroek BA (1993) Treatment of schizophrenia — a clinical and preclinical evaluation of neuroleptic drugs. Pharmacol Ther 57: 1–78

    PubMed  Google Scholar 

  • Fibiger HC, Fibiger HP, Zis AP (1973) Attenuation of amphetamine-induced motor stimulation and stereotypy by 6-hydroxydopamine in the rat. Br J Pharmacol 47: 683–692

    PubMed  Google Scholar 

  • Fink JS, Smith GP (1980) Relationships between selective denervation of dopamine terminal fields in the anterior forebrain and behavioral responses to amphetamine and apomorphine. Brain Res 201: 107–127

    PubMed  Google Scholar 

  • Freed WJ, Weinberger DR, Bing LA, Wyatt RJ (1980) Neuropharmacological studies of phencyclidine (PCP)-induced behavioral stimulation in mice. Psychopharmacology 71: 291–297

    PubMed  Google Scholar 

  • French ED, Vantini G (1984) Phencyclidine-induced locomotor activity in the rat is blocked by 6-hydroxydopamine lesion of the nucleus accumbens: comparisons to other psychomotor stimulants. Psychopharmacology 82: 83–88

    PubMed  Google Scholar 

  • Gardiner TW, Iverson DA, Rebec GV (1988) Heterogeneous responses of neostriatal neurons to amphetamine in freely moving rats. Brain Res 463: 268–274

    PubMed  Google Scholar 

  • Haracz JL, Tschanz JT, Greenberg J, Rebec GV (1989) Amphetamine-induced excitations predominate in single neostriatal neurons showing motor-related activity. Brain Res 489: 365–368

    PubMed  Google Scholar 

  • Haracz JL, Tschanz JT, Wang Z, White IM, Rebec GV (1993) Striatal single-unit responses to amphetamine and neuroleptics in freely moving rats. Neurosci Biobehav Rev 17: 1–12

    PubMed  Google Scholar 

  • Jackson DM, Johansson C, Lindgren L-M, Bengtsson A (1994) Dopamine receptor antagonists block amphetamine and phencyclidine-induced motor stimulation in rats. Pharmacol Biochem Behav 48: 465–471

    PubMed  Google Scholar 

  • Javitt DC, Zukin SR (1991) Recent advances in the phencyclindine model of schizophrenia. Am J Psychiatry 148: 1301–1308

    PubMed  Google Scholar 

  • Johnson KM (1983) Phencyclidine: behavioral and biochemical evidence supporting a role for dopamine. Fed Proc 42: 2579–2583

    PubMed  Google Scholar 

  • Kameyama T, Sugimoto A, Yamaguchi K, Hiramatsu M, Furukawa H, Nabeshima T (1988) The relationship between phencyclidine-induced stereotyped behavior and dopamine release using in vivo voltammetry. Res Commun Subst Abuse 9: 89–105

    Google Scholar 

  • Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHD A lesions of the nucleus accumbens and the corpus striatum. Brain Res 94: 507–522

    PubMed  Google Scholar 

  • Kuczenski R, Segal D (1989) Concomitant characterization of behavioral and striatal neurotransmitter response to amphetamine using in vivo microdialysis. J Neurosci 9: 2051–2065

    PubMed  Google Scholar 

  • Laduron PM (1989) Dopamine receptors and neuroleptic drugs. In: Boulton AB, Baker GB, Juorio AV (eds) Neuromethods: drugs as tools in neurotransmitter research, vol 12. Humana Press, Clifton NJ, pp 261–298

    Google Scholar 

  • Lillrank SM, O'Connor WT, Saransaari P, Ungerstedt U (1994) In vivo effects of local and systemic phencyclidine on the extracellular levels of catecholamines and transmitter amino acids in the dorsolateral striatum of anaesthetized rats. Acta Physiol Scand 150: 109–115

    PubMed  Google Scholar 

  • McCullough LD, Salamone JD (1992) Increases in extracellular dopamine levels and locomotor activity after direct infusion of phencyclidine into the nucleus accumbens. Brain Res 577: 1–9

    PubMed  Google Scholar 

  • Megens AAH, Niemegeers CJE, Awouters FHL (1992) Behavioral disinhibition and depression in amphetaminized rats — a comparison of risperidone, ocaperidone and haloperidol. J Pharmacol Exp Ther 260: 160–167

    PubMed  Google Scholar 

  • Miczek KA, Naney M (1994) Psychomotor stimulant effects of d-amphetamine, MDMA and PCP: aggressive and schedule-controlled behavior in mice. Psychopharmacology 115: 358–365

    PubMed  Google Scholar 

  • Moore S, Kenyon P (1994) Atypical antipsychotics, clozapine and sulpiride do not antagonise amphetamine-induced stereotyped locomotion. Psychopharmacology 114: 123–130

    PubMed  Google Scholar 

  • Murray TF, Horita A (1979) Phencyclidine-induced stereotyped behaviour in rats: dose-response effects and antagonism by neuroleptics. Life Sci 24: 2217–2226

    PubMed  Google Scholar 

  • Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, New York, 91pp

    Google Scholar 

  • Pennartz CMA, Boeijinga PH, Kitai ST, Lopes da Silva FH (1991) Contribution of NMDA receptors to postsynaptic potentials and paired-pulse facilitation in identified neurons of the rat nucleus accumbens in vitro. Exp Brain Res 86: 190–198

    PubMed  Google Scholar 

  • Pierce RC, Rebec GV (1994) Iontophoresis in the neostriatum of awake, unrestrained rats: differential effects of dopamine, glutamate, and ascorbate on motor- and nonmotor-related neurons. Neuroscience (in press)

  • Rebec GV (1992) Neuropharmacology of amphetamine: changes in the activity of striatal neurons during behavior. In: Watson RR (ed) Drugs of abuse and neurobiology. CRC Press, Boca Raton FL, pp 149–174 (CRC Series Physiology of Drug Abuse)

    Google Scholar 

  • Rebec GV, Bashore TR (1984) Critical issues in assessing the behavioral effects of amphetamine. Neurosci Biobehav Rev 8: 153–159

    PubMed  Google Scholar 

  • Rebec GV, Curtis SD (1988) Reciprocal zones of excitation and inhibition in the neostriatum. Synapse 2: 633–635

    PubMed  Google Scholar 

  • Rebec GV, Langley PE, Pierce RC, Wang Z, Heidenreich BA (1993) A simple micromanipulator for multiple uses in freely moving rats: electrophysiology, voltammetry, and simultaneous intracerebral infusions. J Neurosci Meth 47: 53–59

    Google Scholar 

  • Reynolds GP (1994) Antipsychotic drug mechanisms and neurotransmitter systems in schizophrenia. Acta Physiol Scand 89: 36–40

    Google Scholar 

  • Ridley RM, Baker HF, Scraggs PR (1979) The time course of the behavioral effects of amphetamine and their reversal by haloperidol in a primate species. Biol Psychiatry 14: 753–765

    PubMed  Google Scholar 

  • Robbins TW, Sahakian BJ (1983) Behavioral effects of psychomotor stimulant drugs: clinical and neuropsychological implications. In: Creese I (ed) Stimulants: neurochemical, behavioral, and clinical perspectives. Raven Press, New York, pp 301–338

    Google Scholar 

  • Roberts PJ, Anderson SD (1979) Stimulatory effect of L-glutamate and related amino acids on (3H)dopamine release from rat striatum: an in vitro model for glutamate actions. J Neurochem 32: 1539–1545

    PubMed  Google Scholar 

  • Rollema H, Westerink BHC, Grol CJ (1976) Correlation between neuroleptic-induced suppession of stereotyped behaviour and HVA concentrations in rat brain. J Pharm Pharmacol 28: 321–323

    PubMed  Google Scholar 

  • Rosa-Kenig A, Puotz JK, Rebec GV (1993) Involvement of D1 and D2 dopamine receptors in amphetamine-induced changes in striatal activity in behaving rats. Brain Res 619: 347–351

    PubMed  Google Scholar 

  • Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32: 229–313

    PubMed  Google Scholar 

  • Seeman P, Van Tol HHM (1994) Dopamine receptor pharmacology. Trends Pharmacol Sci 15: 264–270

    PubMed  Google Scholar 

  • Seiden LS, Sabol KE, Ricaurte GA (1993) Amphetamine: effects on catecholamine systems and behavior. Ann Rev Pharmacol Toxicol 32: 639–677

    Google Scholar 

  • Skirboll LR, Bunney BS (1979) The effects of acute and chronic haloperidol treatment on spontaneously firing neurons in the caudate nucleus of the rat. Life Sci 25: 1419–1434

    PubMed  Google Scholar 

  • Snyder SH (1988) Psychotogenic drugs as models for schizophrenia. Comments on “The current status of the dopamine hypothesis of schizophrenia.” Neuropsychopharmacology 1: 197–199

    PubMed  Google Scholar 

  • Steinpreis RE, Salamone JD (1993) The role of nucleus accumbens dopamine in the neurochemical and behavioral effects of phencyclidine — a microdialysis and behavioral study. Brain Res 612: 263–270

    PubMed  Google Scholar 

  • Steinpreis RE, Sokolowski JD, Papanikolaou A, Salamone JD (1994) The effects of haloperidol and clozapine on PCP- and amphetamine-induced suppression of social behavior in the rat. Pharmacol Biochem Behav 47: 579–585

    PubMed  Google Scholar 

  • Sturgeon RD, Fessler RG, London SF, Meltzer HY (1981) A comparison of the effects of neuroleptics on phencyclidine-induced behaviors in the rat. Eur J Pharmacol 76: 37–53

    PubMed  Google Scholar 

  • Sturgeon RD, Fessler RG, Meltzer HY (1979) Behavioral rating scales assessing phencyclidine-induced locomotor activity, stereotyped behavior and ataxia in rats. Eur J Pharmacol 59: 169–179

    PubMed  Google Scholar 

  • Tschanz JT, Rebec GV (1988) Atypical antipsychotic drugs block selective components of amphetamine-induced stereotypy. Pharmacol Biochem Behav 31: 519–522

    PubMed  Google Scholar 

  • Tschanz JT, Griffith KG, Haracz JL, Rebec GV (1994) Cortical lesions attenuate the neuronal effects of amphetamine and haloperidol in the neostriatum of freely moving rats. Eur J Pharmacol 257: 161–167

    PubMed  Google Scholar 

  • Tschanz JT, Haracz JL, Griffith KE, Rebec GV (1991) Bilateral cortical ablations attenuate amphetamine-induced excitations of neostriatal motor-related neurons in freely moving rats. Neurosci Lett 134: 127–130

    PubMed  Google Scholar 

  • Vickroy TW, Johnson KM (1982) Similar dopamine-releasing effects of phencyclidine and nonamphetamine stimulants in striatal slices. J Pharmacol Exp Ther 223: 669–674

    PubMed  Google Scholar 

  • Wang Z, Rebec, GV (1993) Neuronal and behavioral correlates of intrastriatal infusions of amphetamine in freely moving rats. Brain Res 627: 79–88

    PubMed  Google Scholar 

  • Wang Z, Haracz JL, Rebec GV (1992) BMY-14802, a sigma ligand and potential antipsychotic drug, reverses amphetamine-induced changes in neostriatal single-unit activity in freely moving rats. Synapse 12: 312–321

    PubMed  Google Scholar 

  • West MO, Michael AJ, Knowles SE, Chapin JK, Woodward DJ (1987) Striatal unit activity and the linkage between sensory and motor events. In: Schneider JS, Lidsky TI (eds) Basal ganglia and behavior: sensory aspects of motor functioning. Hans Huber, Toronto, pp 27–35

    Google Scholar 

  • White IM, Christensen JR, Flory GS, Miller DW, Rebec GV (1994) Amphetamine, cocaine, and dizocilpine enhance performance on a lever-release, conditioned avoidance response task in rats. Psychopharmacology (in press)

  • Wong EHF, Knight AR, Woodruff GN (1988) [3H]MK-801 labels a site on the N-methyl- D-aspartate receptor channel complex in rat brain membranes. J Neurochem 50: 274–281

    PubMed  Google Scholar 

  • Zetterström T, Sharp T, Marsden CA, Ungerstedt U (1983) In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes after d-amphetamine. J Neurochem 41: 1769–1773

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. G. V. Rebec

    Present address: Program in Neural Science, Department of Psychology, Indiana University, Bloomington, USA

  2. I. M. White

    Present address: Laboratory of Neurophysiology, NIMH, 20836, Poolseville, MD, USA

Authors and Affiliations

  1. Program in Neural Science, Department of Psychology, Indiana University, Bloomington, USA

    I. M. White, G. S. Flory, K. C. Hooper, J. Speciale & D. A. Banks

Authors
  1. I. M. White
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. S. Flory
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. C. Hooper
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Speciale
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. A. Banks
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. V. Rebec
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

White, I.M., Flory, G.S., Hooper, K.C. et al. Phencyclidine-induced increases in striatal neuron firing in behaving rats: reversal by haloperidol and clozapine. J. Neural Transmission 102, 99–112 (1995). https://doi.org/10.1007/BF01276506

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01276506

Keywords

Search

Navigation