Abstract
The psychotomimetic actions of the partial-agonist analgesic drugs cyclazocine and levallophan have been demonstrated using a quantitative behavioural test in young rats which measures lateral head movements and pivoting on the hind paws. This drug induced behaviour is antagonized by low doses of the dopaminergic agonists apomorphine and piribedil, the dopamine releasing drug amphetamine, the dopamine reuptake blocking agent benztropine and by large doses of the dopamine precursor l-Dopa. Naloxone antagonizes the behaviour, but only at one hundred times the analgesic antagonist dose. These results show that dopaminergic systems are implicated in the mechanism of action of partial-agonist induced psychotomimetic side effects.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aghajanian, G. K., Bunney, B. S.: Central dopaminergic neurons: neurophysiological identification and responses to drug. In: Frontiers in catecholamine research, E. Usdin and S. Snyder, eds., pp. 643–648. Elmford-New York: Pergamon Press 1973
Andén, N.-E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)
Angrist, B., Gershon, S.: Behavioural profile of a potent new psychotoxic compound. Psychopharmacologia (Berl.) 30, 109–116 (1973)
Ayhan, I. H., Randrup, A.: Inhibitory effects of amphetamine, l-Dopa and apomorphine on morphine-induced behavioural excitation of rats. Arch. int. Pharmacodyn. 204, 283–292 (1973)
Broekkamp, C. L. E., Pijnenburg, A. J. J., van Rossum, J. M.: Dopaminergic transmission in relation to mechanisms underlying stereotyped behaviour. In: Frontiers in catecholamine research, E. Usdin and S. Snyder, eds., pp. 675–676. Elmford-New York: Pergamon Press 1973
Buckett, W. R., Shaw, J. S.: Mechanism for the production of psychotomimetic side-effects by partial-agonist analgesic agents. J. Pharmacol. (Paris) 5, Suppl. 2, 12 (1974)
Carlsson, A., Engel, J., Strömbom, U., Svensson, T. H., Waldeck, B.: Suppression by dopamine-agonists of the ethanol-induced stimulation of locomotor activity and brain dopamine synthesis. Naunyn-Schmiedeberg's Arch. Pharmacol. 283, 117–128 (1974)
Collier, H. O. J., Schneider, C.: Some agonist and antagonist properties of morphine antagonists in rodents. In: Agonist and antagonist actions of narcotic analgesic drugs, H. W. Kosterlitz, H. O. J. Collier, and J. E. Villareal, eds., pp. 128–135. London: Macmillan 1972
Costa, E., Gropetti, A., Revuelta, A.: Action of fenfluramine on monoamine stores of rat tissues. Brit. J. Pharmacol. 41, 57–64 (1971)
Fink, M., Freedman, A. M., Resnick, R., Zaks, A.: Clinical status of the narcotic antagonists in opiate dependence. In: Agonist and antagonist actions of narcotic analgesic drugs, H. W. Kosterlitz, H. O. J. Collier, and J. E. Villareal, eds., pp. 266–276. London: Macmillan 1972
Haertzen, C. A.: Subjective effects of narcotic antagonists cyclazocine and nalorphine on the Addiction Research Centre Inventory (ARCI). Psychopharmacologia (Berl.) 18, 366–377 (1970)
Holtzman, S. G., Jewett, R. E.: Stimulation of behaviour in the rat by cyclazocine: Effects of naloxone. J. Pharmacol. exp. Ther. 187, 380–390 (1973)
Iversen, L. L.: Neuronal and extraneuronal catecholamine uptake mechanisms. In: Frontiers in catecholamine research, E. Usdin and S. Snyder, eds., pp. 403–408. Elmford-New York: Pergamon Press 1973
Jasinski, D. R., Martin, W. R., Sapira, J. D.: Antagonism of the subjective, behavioural, pupillary and respiratory depressant effects of cyclazocine by naloxone. Clin. Pharmacol. Ther. 9, 215–222 (1968)
Kuschinsky, K., Hornykiewicz, O.: Effects of morphine on striatal dopamine metabolism: possible mechanism of its opposite effect on locomotor activity in rats and mice. Europ. J. Pharmacol. 26, 41–50 (1974)
Lasagna, L., Beecher, H. K.: The analgesic effectiveness of nalorphine and nalorphine-morphine combinations in man. J. Pharmacol. exp. Ther. 112, 356–363 (1954)
Maugh, T. H.: Narcotic antagonists: the search accelerates. Science 177, 249–250 (1972)
Persson, T., Waldeck, B.: Further studies on the possible interaction between dopamine and noradrenaline containing neurones in the brain. Europ. J. Pharmacol. 11, 315–320 (1970)
Schneider, C. L.: Behavioural effects of some morphine antagonists and hallucinogens in the rat. Nature (Lond.) 220, 586–587 (1968)
Wood, A. J. J., Moir, D. C., Campbell, C., Davidson, J. F., Gallon, S. C., Henney, E., McAllion, S.: Central nervous system effects of pentazocine. Brit. med. J. 1974I, 205–207
Wray, S. R.: A correlative evaluation of cyclazocine, L.S.D. and naloxone on continuous discriminated avoidance in rats. Psychopharmacologia (Berl.) 26, 29–43 (1972)
Wray, S. R.: Interaction of stress and psychotomimetic drug action: Possible implication for psychosis. Psychopharmacologia (Berl.) 30, 263–268 (1973)
Wray, S. R., Cowan, A.: The behavioural effects of levallorphan, cyprenorphine (M285) and amphetamine on repeated Y-maze performance in rats. Psychopharmacologia (Berl.) 21, 257–267 (1971)
Wray, S. R., Cowan, A. L.: The effects of naloxone, chlorpromazine and haloperidol pretreatment on levallorphan-induced disruption of rats' operant behaviour. Psychopharmacologia (Berl.) 22, 261–270 (1971a)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Buckett, W.R., Shaw, J.S. Dopaminergic drugs antagonize the psychotomimetic effects of partial-agonist analgesics. Psychopharmacologia 42, 293–297 (1975). https://doi.org/10.1007/BF00421271
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00421271