Skip to main content
Log in

Behavioral supersensitivity to apomorphine following chronic narcotic treatment in the guinea pig

  • Published:
Psychopharmacology Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Male albino guinea pigs were treated for 3 weeks with methadone, morphine, haloperidol, or saline. One week and 5 weeks following termination of treatment they were challenged with the directly acting dopaminergic agonist apomorphine. At the week 1 test the haloperidol and saline groups did not differ, but behavioral supersensitivity was apparent in significantly elevated mean stereotypy scores of the methadone and morphine groups relative to the saline group. The source of differences in mean scores was a higher peak score rather than increased duration of action. At the week 5 test the scores of the methadone group were even higher, the morphine group's scores were equivalent to the saline group's, and the haloperidol group's scores were significantly depressed. This study indicates that a 3-week treatment period with methadone or morphine is sufficient to induce dopaminergic supersensitivity and suggests that there may be different time courses for the retention or expression of supersensitivity following these narcotics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ahtee, L.: Catalepsy and stereotypies in rats treated with methadone: relation to striatal dopamine. Eur. J. Pharmacol. 27, 221–230 (1974)

    Google Scholar 

  • Andén, N.-E., Rubenson, A., Fuxe, K., Hokfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)

    Google Scholar 

  • Carlson, K. R., Almasi, J.: Sensitivity to apomorphine in the guinea pig as a function of age and body weight. Psychopharmacology 57, 279–282 (1978)

    Google Scholar 

  • Carlson, K. R., Eibergen, R. D.: Susceptibility to amphetamine-elicited dyskinesias following chronic methadone treatment in monkeys. Ann. N. Y. Acad. Sci. 281, 336–349 (1976)

    Google Scholar 

  • Costall, B., Naylor, R. J.: On catalepsy and catatonia and the predictability of the catalepsy test for neuroleptic activity. Psychopharmacologia (Berl.) 34, 233–241 (1974)

    Google Scholar 

  • Crane, G. E., Paulson, G.: Involuntary movements in a sample of chronic mental patients and their relation to the treatment with neuroleptics. Int. J. Neuropsychiatry 3, 286–291 (1967)

    Google Scholar 

  • Creese, I., Burt, D. R., Snyder, S. H.: Dopamine receptor binding predicts clinical and pharmacological potencies of antischizoprenic drugs. Science 192, 481–483 (1976)

    Google Scholar 

  • Eibergen, R. D., Carlson, K. R.: Behavioral evidence for dopaminergic supersensitivity following chronic treatment with methadone or chlorpromazine in the guinea pig. Psychopharmacology 48, 139–146 (1976a)

    Google Scholar 

  • Eibergen, R. D., Carlson, K. R.: Dyskinesias in monkeys: interaction of methamphetamine with prior methadone treatment. Pharmacol. Biochem. Behav. 5, 175–187 (1976b)

    Google Scholar 

  • Eidelberg, E., Erspamer, R.: Dopaminergic mechanisms of opiate actions in brain. J. Pharmacol. Exp. Ther. 192, 50–57 (1975)

    Google Scholar 

  • Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia (Berl.) 10, 316–323 (1967)

    Google Scholar 

  • Fjalland, B., Moller-Nielsen, I.: Enhancement of methylphenidate-induced stereotypies by repeated administration of neuroleptics. Psychopharmacologia (Berl.) 34, 105–109 (1974)

    Google Scholar 

  • Gerlach, J., Reisby, N., Randrup, A.: Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia (Berl.) 34, 21–35 (1974)

    Google Scholar 

  • Gianutsos, G., Hynes, M. D., Puri, S. K., Drawbaugh, R. B., Lal, H.: Effect of apomorphine and nigrostriatal lesions on aggression and striatal dopamine turnover during morphine with-drawal: evidence for dopaminergic supersensitivity in protracted abstinence. Psychopharmacologia (Berl.) 34, 37–44 (1974)

    Google Scholar 

  • Klawans, H. L., Jr., Rubovits, R.: An experimental model of tardive dyskinesia. J. Neural Trans. 33, 235–246 (1972)

    Google Scholar 

  • Kreek, M. J., Gutjahr, C. L., Garfield, J. W., Bowen, D. V., Field, F. H.: Drug interactions with methadone. Ann. N. Y. Acad. Sci. 281, 350–371 (1976)

    Google Scholar 

  • Lal, S., Feldmuller, F.: Effect of amphetamine and apomorphine on brain monoamines and behavior in the immature and young adult rat. Arch. Int. Pharmacodyn. 218, 239–251 (1975)

    Google Scholar 

  • Moffett, A. D., Soloway, I. H., Glick, M. X.: Post-treatment behavior following ambulatory detoxification. In: Methadone: experiences and issues, C. D. Chambers and L. Brill, eds., pp. 215–227. New York: Behavioral Publications 1973

    Google Scholar 

  • Perez-Cruet, J., Di Chiara, G., Gessa, G. L.: Accelerated synthesis of dopamine in the rat brain after methadone. Experientia 28, 926 (1972)

    Google Scholar 

  • Puri, S. K., Lal, H.: Effect of dopaminergic stimulation or blockade on morphine-withdrawal aggression. Psychopharmacologia (Berl.) 32, 113–120 (1973)

    Google Scholar 

  • Puri, S. K., Reddy, C., Lal, H.: Blockade of central dopaminergic receptors by morphine: effect of haloperidol, apomorphine or benztropine. Res. Commun. Chem. Path. Pharmacol. 5, 389–401 (1973)

    Google Scholar 

  • Sasame, H. A., Perez-Cruet, J., Di Chiara, G., Tagliamonte, A., Tagliamonte, P., Gessa, G. L.: Evidence that methadone blocks dopamine receptors in the brain. J. Neurochem. 19, 1953–1957 (1972)

    Google Scholar 

  • Sayers, A. C., Burki, H. R., Ruch, W., Asper, H.: Neuroleptic-induced hypersensitivity of striatal dopamine receptors in the rat as a model of tardive dyskinesias. Effects of clozapine, haloperidol, loxapine and chlorpromazine. Psychopharmacologia (Berl.) 41, 97–104 (1975)

    Google Scholar 

  • Srimal, R. C., Dhawan, B. N.: An analysis of methylphenidate induced gnawing in guinea pigs. Psychopharmacologia (Berl.) 18, 99–107 (1970)

    Google Scholar 

  • Tarsy, D., Baldessarini, R. J.: Behavioral supersensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic function of catecholamines. Neuropharmacology 13, 927–940 (1974)

    Google Scholar 

  • Tarsy, D., Baldessarini, R. J.: The tardive dyskinesia syndrome. In: Clinical neuropharmacology, vol. 1, H. L. Klawans Jr., ed., pp. 29–61. New York: Raven Press 1976

    Google Scholar 

  • Teiger, D. G.: A test for antinociceptive activity of narcotic and narcotic antagonist analgesics in the guinea pig. J. Pharm. Exp. Ther. 197, 311–316 (1976)

    Google Scholar 

  • Ungerstedt, U., Butcher, L. L., Butcher, S. G., Andén, N.-E., Fuxe, K.: Direct chemical stimulation of dopaminergic mechanisms in the neostriatum of the rat. Brain Res. 14, 461–471 (1969)

    Google Scholar 

  • Winer, B. J.: Statistical principles in experimental design, 2nd ed. New York: McGraw-Hill 1971

    Google Scholar 

  • York, D. H.: Dopamine receptor blockade—a central action of chlorpromazine on striatal neurons. Brain Res. 37, 91–99 (1972)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carlson, K.R., Almasi, J. Behavioral supersensitivity to apomorphine following chronic narcotic treatment in the guinea pig. Psychopharmacology 57, 273–277 (1978). https://doi.org/10.1007/BF00426750

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00426750

Key words

Navigation