Abstract
Some atypical neuroleptics have been shown to exert selective effects on the nigrostriatal or mesolimbic dopamine systems as assessed by behavioral, biochemical and electrophysiological measures. This specificity appears to occur using chronic or acute schedules of drug administration. This study examined the effect of chronic administration of haloperidol, clozapine, sulpiride and metoclopramide on stereotypy and locomotor activity elicited by direct injection of dopamine in to the striatum or nucleus accumbens, respectively. Each rat was pre-treated with a neuroleptic drug or vehicle control for 21 days. Five days after the termination of drug treatment, each rat was injected with 10 μg dopamine bilaterally, and stereotypy or locomotor activity was measured. Rats pre-treated with metoclopramide exhibited an enhanced stereotypy response, and rats pre-treated with haloperidol, clozapine or sulpiride exhibited enhanced locomotor activity compared to controls. The extent to which these results demonstrate the selective action of these drugs in sensitizing dopamine systems is discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Blaha CD, Lane RF (1985a) Chronic antipsychotic drug effects on dopamine release in vivo: regional specificity and mechanisms of action. Neurosci Abstr 11:499
Blaha CD, Lane RF (1985b) In vivo release of dopamine in striatal and limbic regions after chronic administration of neuroleptic drugs. Fed Proc 44:892
Blaha CD, Lane RF (1987) Chronic treatment with classical and atypical antipsychotic drugs differentially decreases dopamine release in striatum and nucleus accumbens in vivo. Neurosci Let 78:199–204
Borison RL, Diamond BI (1983) Regional selectivity of neuroleptic drugs: an argument for site specificity. Brain Res Bull 11:215–218
Burt DR, Creese I, Snyder SH (1977) Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science 196:326–328
Chiodo LA, Bunney BS (1983) Typical and atypical neuroleptics: differential effects of chronic administration on the activity of A9 and A10 midbrain dopaminergic neurons. J Neurosci 3:1607–1619
Costall B, Naylor RJ (1976) A comparison of the abilities of typical neuroleptic agents and of thioridizine, clozapine, sulpiride and metoclopramide to antagonize the hyperactivity induced by dopamine applied intracerebrally to areas of the extrapyramidal and mesolimbic systems. Eur J Pharmacol 40:9–19
Creese I, Iversen SD (1975) The pharmacological and anatomical substrates for the amphetamine response in the rat. Brain Res 83:419–436
Creese I, Burt DR, Snyder SH (1977) Dopamine receptor binding enhancement accompanies lesion-induced behavioral supersensitivity. Science 197:596–598
Davis KD, Hollister LE, Fritz WE (1978) Induction of dopaminergic mesolimbic receptor supersensitivity by haloperidol. Life Sci 23:1543–1548
Deutsch SI, Halperin R, Stanley M, Davis KL (1985) Effect of chronic haloperidol and quinacrine coadministration on striatal HVA levels and stereotypic behaviors in response to apomorphine in the rat. Neurochem Res 10:491–498
Fog R, Pakkenberg H (1971) Behavioral effects of dopamine and p-hydroxyamphetamine injected into corpus striatum of rats. Exp Neurol 31:75–86
Gnegy ME, Lucchelli A, Costa E (1977) Correlation between drug-induced supersensitivity of dopamine dependent striatal mechanisms and the increase in striatal content of the Ca+ regulated protein activator of cAMP phosphodiesterase. Naunyn-Schmiedeberg's Arch Pharmacol 301:121–127
Grace AA, Bunney BS (1986) Induction of depolarization block in midbrain dopamine neurons by repeated administration of haloperidol: analysis using in vivo intracellular recording. J Pharmacol Exp Ther 238:1092–1100
Halperin R, Guerin JJ, Davis KL (1983) Chronic administration of three neuroleptics: effects of behavioral supersensitivity mediated by two different brain regions in the rat. Life Sci 33:585–592
Hodge GK, Boyeson MG, Linn RT (1981) Dopaminergic agonists differentially affect open-field activity of rats with A10 lesions. Psychopharmacology 73:39–42
Jackson DM, Anden NE, Engel J, Liljequist S (1975) The effect of long-term penfluridol treatment on the sensitivity of the dopamine receptors in the nucleus accumbens and in the corpus striatum. Psychopharmacologia 45:151–155
Koenig JFR, Klippel RA (1963) The rat brain: a stereotaxic atlas. Williams & Wilkins, Baltimore
Kohler C, Ogren S, Fuxe K (1984) Studies on the mechanism of action of substituted benzamide drugs. Acta Psychiatr Scand [Suppl 311] 69:125–137
Lautin A, Wazer D, Stanley M, Rotrosen J, Gershon S (1980) Chronic treatment with metoclopramide induces behavioral supersensitivity to apomorphine and enhances specific binding of 3H-spiroperidol to rat striata. Life Sci 27:305–316
Leysen JE (1980) 3H-apomorphine receptors in various rat brain regions: a study of specific and non-specific binding and the influence of chronic neuroleptic treatment. Adv Biochem Psychopharmol 24:123–132
Lindvall O, Bjorklund A (1974) The organization of the ascending catecholamine neuron systems in the rat brain. Acta Physiol Scand [Suppl] 412:1–48
Muller P, Seeman P (1978) Dopaminergic supersensitivity after neuroleptics: time course and specificity. Psychopharmacology 60:1–11
Murugaiah K, Mann S, Theordorou AE, Jenner P, Marsden CD (1982) Increased striatal acetylcholine after 14 months cis-flupenthixol treatment in rats suggests functional supersensitivity of dopamine receptors. Life Sci 31:181–188
Pijnenburg AJ, van Rossum JM (1973) Letter: stimulation of locomotor activity following injection of dopamine into the nucleus accumbens. J Pharm Pharmacol 25:1003–1004
Pijnenburg AJ, Honig WM, van Rossum JM (1975) Effects of antagonists upon locomotor stimulation induced by injection of dopamine and noradrenaline into the nucleus accumbens of nialamide pre-treated rats. Psychopharmacologia 41:175–180
Pijnenburg AJ, Honig WM, van der Heyden JAM, vanRossum JM (1976) Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. Eur J Pharmacol 35:45–58
Siegel S (1956) Nonparametric statistics for the behavioral sciences. McGraw-Hill, New York
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
White FJ, Wang RY (1983) Differential effects of classical and atypical antipsychotic drugs on A9 and A10 dopamine neurons. Science 221:1054–1057
Winer BJ (1971) Statistical principles in experimental design, 2nd edn. McGraw-Hill, New York
Author information
Authors and Affiliations
Additional information
Work carried out at Psychiatry Service, Bronx Veterans Administration Hospital and Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA
Rights and permissions
About this article
Cite this article
Halperin, R., Guerin, J.J. & Davis, K.L. Regional differences in the induction of behavioral supersensitivity by prolonged treatment with atypical neuroleptics. Psychopharmacology 98, 386–391 (1989). https://doi.org/10.1007/BF00451692
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00451692