Skip to main content
Log in

Tolerance to or facilitation of pharmacological effects induced by chronic treatment with the beta-adrenergic stimulant clenbuterol

  • Original Papers
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

The effect in mice of chronic administration of the beta-adrenergic agonist clenbuterol was studied using four pharmacological tests, two of which are predictive of antidepressant activity in man. The suppressive effect of acute administration of the beta-adrenergic agonist in two tests unrelated to antidepressant activity, locomotor activity and investigation of food, was attenuated after chronic treatment. However, in the two tests which are predictive of antidepressant activity, antagonism of reserpine induced hypothermia and potentiation of yohimbine toxicity, the effect of clenbuterol was greater following chronic treatment.

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

  • Abbrachio, M. P., Cattabeni, F., Coen, E., Torres-Hernandez, Y., Omini, C.: Beta-adrenoceptor desensitization in rat lung; functional and biochemical aspects. Eur. J. Pharmacol.89, 35–42 (1983).

    PubMed  Google Scholar 

  • Banerjee, S. P., Rung, L. S., Riggi, S. J., Chanda, S. K.: Development of beta-adrenergic receptor subsensitivity by antidepressants. Nature268, 455–456 (1977).

    PubMed  Google Scholar 

  • Bergstrom, D. A., Kellar, K. J.: Adrenergic and serotonergic receptor binding in rat brain after chronic desmethylimipramine treatment. J. Pharmacol. Exp. Ther.209, 256–261 (1979).

    PubMed  Google Scholar 

  • Boissier, J. R., Simon, P., Lwoff. J. M.: L'utilisation d'une réaction particulière d'exploration de la Souris pour l'étude des médicaments psychotropes. Thérapie19, 571–583 (1964).

    Google Scholar 

  • Borsini, F., Bendotti, C., Thurlby, P., Samanin, R.: Evidence that systemically administered salbutamol reduces food-intake in rats by acting on central beta-adrenergic sites. Life Sci.30, 905–911 (1982).

    PubMed  Google Scholar 

  • Bourin, M., Poncelet, M., Chermat, R., Simon, P.: The value of the reserpine test in psychopharmacology. Arzneim.-Forsch./Drug Res.33, 1175–1176 (1983).

    Google Scholar 

  • Bretz, U., Martin, U., Mazzoni, L., Ney, U. M.: Beta-adrenergic tachyphylaxis in the rat and its reversal and prevention by ketotifen. Eur. J. Pharmacol.86, 321–328 (1983).

    PubMed  Google Scholar 

  • Conolly, M. F., Davies, D. S., Dollery, C. T., George, C. F.: Resistance to beta-adrenoceptor stimulants (a possible explanation for the rise in asthma deaths). Br. J. Pharmacol.43, 389–402 (1971).

    PubMed  Google Scholar 

  • Dibner, M. D., Molinoff, P. B.: Agonist induced changes in beta-adrenergic receptor density and receptor-mediated responsiveness in slices of rat cerebral cortex. J. Pharmacol. Exp. Ther.210, 433–439 (1979).

    PubMed  Google Scholar 

  • Diquet, B., Doare, L., Simon, P.: Determination of clenbuterol in the high nanogram range in plasma of mice by H.P.L.C. with amperometric detection. J. Chromato. Biomed. Appl.336, 415–421 (1984).

    Google Scholar 

  • Dooley, D. H., Delini-Stula, A., Mogilnicka, F., Hauser, K., Billiger, H.: Some neurochemical and behavioral effects of clenbuterol a centrally acting beta-adrenergic agonist. 5th CA Symposium, Goteborg 1983, Abstract no. 114, p. 117 (1983).

  • Dooley, D. H., Hauser, L.: Subchronic infusion of clenbuterol: a beta-adrenergic agonist, decreases the cerebellar beta-receptors. Neurosci. Lett.36, 93–97 (1983).

    PubMed  Google Scholar 

  • Douglas, J. S., Lewis, A. J., Ridgway, P., Brink, C., Bouhuys, A.: Tachyphylaxis to beta-adrenoceptor agonists in guinea-pig airway smooth musclein vivo andin vitro. Eur. J. Pharmacol.42, 195–205 (1977).

    PubMed  Google Scholar 

  • Dumeur, G., Hue, B., Mouries, M. A., Lwoff, J. M.: “Tantale” test: simultaneous study of two behaviour patterns in mice. 11th CINP Congress, Vienna, July 9–14, Abstract, p. 235 (1978 a).

  • Dumeur, G., Hue, B., Mouries, M. A., Lwoff, J. M.: Action des médicaments psychotropes sur un test de comportement chez la Souris (test de Tantale). 7th Int. Cong. Pharmacol. IUPHAR, July 16–21, Abstract (1978 b).

  • Francès, H., Puech, A. J., Simon, P.: Profil psychopharmacologique de l'isoprénaline et du salbutamol. J. Pharmacol. (Paris)9, 25–34 (1982).

    Google Scholar 

  • Francès, H., Danti, S., Simon, P.: Test de Tantale, activité motrice et stimulants beta-adrénergiques. J. Pharmacol. (Paris)13, 135 (1982).

    Google Scholar 

  • Francès, H., Danti, S., Puech, A. J., Simon, P.: Disappearance of the decreasing in biting behavior induced by clenbuterol, a beta-adrenergic agonist, after chronic administration. Pharmacol. Biochem. and Behav.21, 313–316 (1984).

    Google Scholar 

  • Goldschmidt, P. L., Francès, H., Simon, P.: Stimulation of beta-adrenergic receptors and spontaneous motor activity in mice. Pharmacol. Biochem. and Behav.21, 177–180 (1984).

    Google Scholar 

  • Hall, H., Sallemark, M., Ross, S. B.: Clenbuterol, a central beta-adrenoceptor agonist. Acta Pharmacol. Toxicol.47, 159–160 (1980).

    Google Scholar 

  • Johansson, S. R. M., Andersson, R. G. G.: Mechanisms of beta-adrenergic desensitization in rat myometrium. Acta Pharmacol. Toxicol.49, 241–247 (1981).

    Google Scholar 

  • Jouvent, R., Ghozlan, A., Puech, A. J., Lecrubier, Y., Simon, P., Widlocher, D.: Étude contrôlée clomipramine/clenbuterol chez les déprimés hospitalisés. Ass. Française de Psychiatrie Biologique, 25 October 1983.

  • Lam, V., Bar, H. P.: Adrenaline-induced desensitization of liver adenylate cyclase. Biochem. Pharmacol.25, 2103–2104 (1976).

    PubMed  Google Scholar 

  • Lecrubier, Y., Puech, A. J., Jouvent, R., Simon, P., Widlocher, D.: A beta-adrenergic stimulant, salbutamol vs clomipramine in depression: a controlled study. Br. J. Psychiat.136, 354–358 (1980).

    Google Scholar 

  • Leibowitz, S. F.: Ingestion in the satiated rat: role of alpha and beta receptors in mediating effects of hypothalamic adrenergic stimulation. Physiol. Behav.14, 743–754 (1975).

    PubMed  Google Scholar 

  • Lerer, B., Ebstein, R. P., Belmaker, R. M.: Subsensitivity of human beta-adrenergic adenylate cyclase after salbutamol treatment of depression. Psychopharmacology75, 169–172 (1981).

    PubMed  Google Scholar 

  • Lin, C. S., Hurwitz, L., Jenne, J., Avner, B. P.: Mechanism of isoproterenol induced desensitization of tracheal smooth muscle. J. Pharmacol. Exp. Ther.203, 12–22 (1977).

    PubMed  Google Scholar 

  • Malik, J. B.: Potentiation of yohimbine-induced lethality in mice: predictor of antidepressant potential. Drug Development Res.3, 357–363 (1983).

    Google Scholar 

  • Mickey, J., Tate, R., Lefkowitz, R. J.: Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (−)isoproterenolin vitro. J. Biol. Chem.250, 5727–5729 (1975).

    PubMed  Google Scholar 

  • Moberg, G. P., Clark, C. R., Robinson, D. W.: Observation on the ontogeny of the feeding response to beta-adrenergic agonists and antagonists. Br. Vet. J.129, 27 (1973).

    PubMed  Google Scholar 

  • Przegalinski, E., Baran, L., Kedrek, G.: The central action of salbutamol, a beta-agonist with a potential antidepressant activity. Pol. J. Pharm. Pharmacol.32, 485–493 (1980).

    Google Scholar 

  • Przegalinski, E., Siwanowicz, J., Bigajska, K., Baran, L.: Chronic treatment with electroconvulsive shock prevents the salbutamol-induced hypoactivity in rats. J. Pharm. Pharmacol.36, 626–628 (1984).

    PubMed  Google Scholar 

  • Przegalinski, E., Baran, L., Siwanowicz, J.: The effect of chronic treatment with antidepressant drugs on salbutamol-induced hypoactivity in rats. Psychopharmacol.80, 355–359 (1983).

    Google Scholar 

  • Ross, S. B.: Antagonism of reserpine-induced hypothermia in mice by some beta-adrenoceptor agonist. Acta Pharmacol. Toxicol.47, 347–350 (1980).

    Google Scholar 

  • Shear, M., Insel, P., Melmon, K. L., Coffino, P.: Agonist-specific refractoriness induced by isoproterenol. Studies with mutant cells. J. Biol. Chem.251, 7572–7576 (1976).

    PubMed  Google Scholar 

  • Simon, P., Lecrubier, Y., Jouvent, R., Puech, A. J., Allilaire, J. F., Widlocher, D.: Experimental and clinical evidence of the antidepressant effect of a beta-adrenergic stimulant. Psychol. Med.8, 335–338 (1978).

    PubMed  Google Scholar 

  • Simon, P., Lecrubier, Y., Jouvent, R., Puech, A. J., Widlocher, D.: Beta-receptor stimulation in the treatment of depression. In: Frontiers in Biochemical and Pharmacological Research in Depression (Usdin, E., et al., eds.), pp. 293–299. New York: Raven Press. 1984.

    Google Scholar 

  • Souto, M., Francès, H., Lecrubier, Y., Puech, A. J., Simon, P.: Antagonism by d,l-propranolol of imipramine effects in mice. Eur. J. Pharmacol.60, 105–108 (1979).

    PubMed  Google Scholar 

  • Svedmyr, N., Larsson, S., Thiringer, G.: Studies of resistance to long-acting adrenergic beta-stimulators in asthmatic patients. Br. Med. J.2, 668 (1974).

    Google Scholar 

  • U'Prichard, D. C., Enna, S. J.: In vitro modulation of CNS beta-receptor number by antidepressants and beta-agonists. Eur. J. Pharmacol.59, 297–301 (1979).

    PubMed  Google Scholar 

  • Widlocher, D., Simon, P., Allilaire, J. F., Jouvent, R., Lecurbier, Y., Puech, A. J.: Une nouvelle approche dans le traitement des états dépressifs: le salbutamol. Ann. Med. Interne129, 419–422 (1978).

    Google Scholar 

  • Willner, P.: The validity of animal models of depression. Psychopharmacol.83, 1–16 (1984).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Francès, H., Diquet, B., Goldschmidt, P. et al. Tolerance to or facilitation of pharmacological effects induced by chronic treatment with the beta-adrenergic stimulant clenbuterol. J. Neural Transmission 62, 65–76 (1985). https://doi.org/10.1007/BF01260416

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01260416

Key words

Navigation