Abstract
Hypodipsia produced by injection of d-amphetamine (2.0 mg/kg) or apomorphine (0.8 mg/kg) in rats, was partially antagonized by two DA-specific neuroleptic drugs, Pimozide and Spiramide, respectively. Pimozide revealed a maximal amphetamine-antagonistic effect at dose levels between 0.1–0.4 mg/kg. Hypodipsia could also be produced by Pimozide alone in doses greater than 1.0 mg/kg. Pretreatment of the apomorphine-induced hypodipsia with 0.05 mg/kg Spiramide also reliably counteracted drinking deficits.
The interaction of water deprivation combined with the presence or absence of food in the test situation was also examined, but no effect was found.
The possibility that perseverative rearing on the hind legs under d-amphetamine might interfere with drinking was tested with high vs. low drinking-tubes in the Pimozide-amphetamine experiments. There was evidence for a slight initial effect of drinking position, but the general form of the dose-response curve was not greatly altered.
It was concluded that dopamine effects cannot easily be excluded from a role in the control of drinking, and that the primary role often accorded norepinephrine in relation to amphetamine effects should be re-examined with respect to the specific behavioural functions which are altered.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andén, N.-E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)
Andén, N.-E., Butcher, S. C., Corrodi, H., Fuxe, F., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol. 11, 303–314 (1970)
Andén, N.-E., Corrodi, H., Fuxe, K., Ungerstedt, U.: Action of neuroleptics on the nigro-neostriatal DA pathway. Proceedings: Congress International Neuropsychopharmacologicum, Copenhagen, August 1972. Abstracts, p. 19
Bridges, T. E., Thorn, N. A.: The effect of autonomic blocking agents on vaso-pressin release in vivo induced by osmoreceptor stimulation. J. Endocr. 48, 265–276 (1970)
Buerger, P. B., Levitt, R. A., Irwin, D. A.: Chemical stimulation of the brain: Relationship between neural activity and water ingestion in the rat. J. comp. physiol. Psychol. 82, 278–285 (1973)
Epstein, A. N., Spector, D., Samman, A., Goldblum, C.: Exaggerated prandial drinking in the rat without salivary glands. Nature (Lond.) 201, 1342–1343 (1964)
Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia (Berl.) 10, 316–323 (1967)
Fisher, A. E., Coury, J. N.: Cholinergic tracing of a central neural circuit underlying the thirst drive. Science 138, 691–693 (1962)
Friedman, E., Starr, N., Gershon, S.: Catecholamine synthesis and the regulation of food intake in the rat. Life Sci. 12, 317–326 (1973)
Glick, S. D., Muller, R. U.: Paradoxical effects of low doses of d-amphetamine in rats. Psychopharmacologia (Berl.) 22, 396–402 (1971)
Grossman, S. P.: Eating or drinking elicited by direct adrenergic or cholinergic stimulation of the hypothalamus. Science 132, 301–302 (1960)
Holtzman, S. G., Jewett, R. E.: The role of brain norepinephrine in the anorexic effects of dextroamphetamine and monoamine oxidase inhibitors in the rat. Psychopharmacologia (Berl.) 22, 151–161 (1971)
Janssen, P. A. J., Niemegeers, C. J. E., Schellekens, K. H. L.: Is it possible to predict the clinical effects of neuroleptic drugs (major tranquillizers) from animal data? (Part IV). Arzneimittel-Forsch. (Drug Res.) 17, 841–854 (1967)
Lyon, M., Randrup, A.: The dose-response effect of amphetamine upon avoidance behaviour in the rat seen as a function of increasing stereotypy. Psychopharmacologia (Berl.) 23, 334–347 (1972)
Maickel, R. P., Cox, R. H., Jr., Ksir, C. J., Snodgrass, W. R., Miller, F. P.: Some aspects of the behavioural pharmacology of the amphetamines. In: Amphetamines and related compounds, pp. 747–759, E. Costa and S. Garattini, Eds. New York: Raven Press 1970
Mantegazza, P., Naimzada, K. M., Riva, M.: Effects of propranolol on some activities of amphetamine. Europ. J. Pharmacol. 4, 25–30 (1968)
Neill, D. B., Grossman, S. P.: Interaction of the effects of reserpine and amphetamine on food and water intake. J. comp. physiol. Psychol. 76, 327–336 (1971)
Papeschi, R., Randrup, A.: Catalepsy, sedation and hypothermia induced by α-methyl-p-tyrosine in the rat. Pharmakopsychiat.-Neuropharmak. (Stuttg.) (in press)
Poschel, B. P. H.: Effects of methamphetamine on hunger and thirst motivated variable-interval performance. J. comp. physiol. Psychol. 56, 968–973 (1973)
Roos, B.-E.: Decrease in homovanillic acid as evidence for dopamine receptor stimulation by apomorphine in the neostriatum of the rat. J. Pharm. Pharmacol. 21, 263–264 (1969)
Scheel-Krüger, J.: Some aspects of the mechanism of action of various stimulant amphetamine analogues. Psychiat. Neurol. Neurochir. (Amst.) 75, 179–192 (1972)
SchiØrring, E.: Amphetamine induced selective stimulation of certain items with concurrent inhibition of others in an open-field test with rats. Behaviour 39, 1–17 (1971)
Soulairac, A., Soulairac, M.-L.: Effects of amphetaminelike substances and L-Dopa on thirst, water intake and diuresis. In: Amphetamines and related compounds, pp. 819–837, E. Costa and S. Garattini, Eds. New York: Raven Press 1970
Spector, S., Sjoerdsma, A., Udenfriend, S.: Blockade of endogenous norepinephrine synthesis by α-methyltyrosine, an inhibitor of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 147, 86–95 (1965)
Teitelbaum, P., Derks, P.: The effects of amphetamine on forced drinking in the rat. J. comp. physiol. Psychol. 51, 801–810 (1958)
Teitelbaum, P., Epstein, A. N.: The lateral hypothalamic syndrome: Recovery of feeding and drinking after lateral hypotalamic lesions. Psychol. Rev. 69, 74–90 (1962)
Tormey, J., Lasagna, L.: Relation of thyroid function to acute and chronic effects of amphetamine in the rat. J. Pharmacol. exp. Ther. 128, 201–209 (1960)
Ungerstedt, U.: Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta physiol. scand., Suppl. 367, 95–122 (1971)
Van Rossum, J.: The significance of dopamine receptor blockade for the action of neuroleptic drugs. In: Neuropsychopharmacology, vol. 5, pp. 321–323, H. Brill, Ed. Int. Congr. Ser. 129. Amsterdam: Excerpta Medica 1967
Weissman, A., Koe, B. K., Tenen, S. S.: Antiamphetamine effects following inhibition of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 151, 339–352 (1966)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nielsen, E.B., Lyon, M. Drinking behaviour and brain dopamine: Antagonistic effect of two neuroleptic drugs (Pimozide and Spiramide) upon amphetamine- or apomorphine-induced hypodipsia. Psychopharmacologia 33, 299–308 (1973). https://doi.org/10.1007/BF00437507
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00437507