Abstract
Different groups of rats were pretreated with the dopamine receptor blocker, pimozide (0.25, 0.5, or 1.0 mg/kg), in an attempt to investigate the role of dopaminergic transmission in the acquisition, maintenance, and extinction of a taste aversion produced by d-amphetamine sulphate (1.0 or 2.0 mg/kg). In the first phase of the experiment, all doses of pimozide attenuated but did not block the acquisition of the aversion produced by 1.0 mg/kg but not by 2.0 mg/kg amphetamine. In Phase II, pimozide pretreatment was suspended to allow the attenuated groups to acquire the aversion and then reintroduced in Phase III. In this phase all groups continued to avoid the taste, indicating a failure of pimozide to affect the maintenance of the avoidance response. When amphetamine treatment was suspended in Phase IV, pimozide accelerated the extinction, especially in those groups that had previously received the 1.0 mg/kg dose of amphetamine. These results are discussed with reference to dopaminergic mechanisms in avoidance learning and a pimozide-mediated reduction in functional strength of amphetamine as an unconditioned stimulus.
Similar content being viewed by others
References
Andén, N.-E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur. J. Pharmacol. 11, 303–314 (1970)
Berger, B. D.: Conditioning of food aversions by injections of psychoative drugs. J. comp. Physiol. psychol. 81, 21–26 (1972)
Brodie, B. B., Cho, A. K., Stefano, F. J. E., Gessa, G. L.: On mechanisms of norepinephrine release by amphetamine and tyramine and tolerance to their effects. In: Advances in biochemical psychopharmacology, E. Costa and P. Greengard, eds., Vol. 1, p. 222. New York: Raven Press 1969.
Cappell, H. D., LeBlanc, A. E.: Conditioned aversion to saccharin by single administrations of mescaline and d-amphetamine. Psychopharmacologia (Berl.) 22, 352–356 (1971)
Carey, R. J.: Long-term aversion to a saccharin solution induced by repeated amphetamine injections. Pharmac. Biochem. Behav. 1, 265–270 (1973)
Carey, R. J., Goodall, E. B.: Amphetamine-induced taste aversion: A comparison of d- versus l-amphetamine. Pharmac. Biochem. Behav. 2, 325–330 (1974)
Carlsson, A.: Amphetamine and brain catecholamines. In: Amphetamines and related compounds. E. Costa and S. Garattini, eds., pp. 289–300. New York: Raven Press 1970
Cooper, B. R., Howard, J. L., Grant, L. D., Smith, R. D., Breese, G. R.: Alteration of avoidance and ingestive behavior after destruction of central catecholamine pathways with 6-hydroxydopamine. Pharmac. Biochem. Behav. 2, 639–649 (1974)
Fibiger, H. C., Phillips, A. G., Zis, A. P.: Deficits in instrumental responding after 6-hydroxydopamine lesions of the nigroneostriatal dopaminergic projection. Pharmac. Biochem. Behav. 2, 87–96 (1973)
Fibiger, H. C., Zis, A. P., Phillips, A. G.: Haloperidol-induced disruption of conditioned avoidance responding: Attenuation by prior training or by anticholinergic drugs. Eur. J. Pharmacol. 30, 309–314 (1975)
Fuxe, K., Ungerstedt, U.: Histochemical, biochemical and functional studies on central monamine neurons after acute and chronic amphetamine administration. In: Amphetamines and related compounds, E. Costa and S. Garattini, eds., pp. 257–288. New York: Raven Press, 1970
Goudie, A. J., Thornton, E. W., Wheatley, J.: Attenuation by alphamethyltyrosine of amphetamine induced conditioned taste aversion. Psychopharmacologia (Berl.) 45, 119–123 (1975)
Grupp, L. A.: Time dependent action of pimozide on deprivation-induced water intake: Evidence for a direct drug effect. Pharmac. Biochem. Behav. 4, 725–728 (1976)
Janssen, P. A. J., Niemegeers, C. J. E., Schellekens, K. H. L., Dresse, A., Lenaerts, F. M., Pinchard, A., Schaper, W. K. A., van Nueten, J. M., Verbruggen, F. J.: Pimozide, a chemically novel, highly potent and orally long-acting neuroleptic drug. Arzneimittel-Forsch. 18, 261–287 (1968)
Lenard, L. G., Beer, B.: Modification of avoidance behavior in 6-hydroxydopamine-treated rats by stimulation of central nor-adrenergic and dopaminergic receptors. Pharmac. Biochem. Behav. 3, 887–893 (1975a)
Lenard, L. G., Beer, B.: Relationship of brain levels of norepinephrine and dopamine to avoidance behavior in rats after intraventricular administration of 6-hydroxydopamine. Pharmac. Biochem. Behav. 3, 895–899 (1975b)
Rech, R. H., Borys, H. K., Moore, K. E.: Alterations in behavior and brain catecholamine levels in rats treated with α-methyltyrosine. J. pharm. exp. Ther. 153, 412–419 (1966)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Grupp, L.A. Effects of pimozide on the acquisition, maintenance, and extinction of an amphetamine-induced taste aversion. Psychopharmacology 53, 235–242 (1977). https://doi.org/10.1007/BF00492357
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00492357