Skip to main content
SpringerLink
Log in

Differential behavioral and biochemical effects of four dopaminergic agonists

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Some behavioral and biochemical effects of four dopaminergic agonists (apomorphine, piribedil, lergotrile, and bromocriptine) were determined in the mouse. As expected, all four drugs dose-dependently reversed the α-methyltyrosine-induced decline of fore-brain dopamine. All four compounds reduced locomotor activity at low doses, but only apomorphine and bromocriptine increased motor activity at higher doses. All four drugs caused some reversal of the baclofen-induced elevation in forebrain dopamine concentrations, but only apomorphine and bromocriptine completely reversed the effects of baclofen. After chronic treatment with haloperidol, the behavioral effects of lergotrile and bromocriptine were altered. Doses of those drugs reducing motor activity in normal animals were ineffective after chronic haloperidol. The latent stimulation induced by bromocriptine was enhanced, while a stimulatory effect of lergotrile emerged in these animals. These effects were noted in conjunction with an enhanced sensitivity to the drug-induced decrease in dopamine turnover. These results demonstrate that dopamine agonists may be differentiated on the basis of certain behavioral and biochemical tests and suggest an interaction of these drugs with two different populations of dopamine receptors.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • 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 

  • Burki, H. R., Asper, H., Ruch, W., Zuger, P. E.: Bromocriptine, dihydroergotoxine, methysergide, d-SD, CF 25–397, and 29–712: Effects on the metabolism of biogenic amines in the brain of the rat. Psychopharmacology 57, 227–237 (1978)

    Google Scholar 

  • Carlsson, A.: Dopaminergic autoreceptors. In: Chemical tools in catecholamine research, vol. II, O. Almgren, A. Carlsson, J. Engel, eds., pp. 219–225. Amsterdam: North Holland 1975

    Google Scholar 

  • Chang, C. C.: A sensitive method for spectrofluormetric assay of catecholamines. Int. J. Neuropharmacol. 3, 643–649 (1964)

    Google Scholar 

  • Clemens, J. A., Shaar, C. J., Smalstig, E. B., Bach, N. J., Korn-feld, E. C.: Inhibition of prolactin secretion by ergolines. Endocrinology 94, 1171–1176 (1974)

    Google Scholar 

  • Cools, A. R., van Rossum, J. M.: Excitation-mediating and inhibition-mediating dopamine receptors: A new concept towards a better understanding of electrophysiological, biochemical, pharmacological, functional and clinical data. Psychopharmacologia 45, 243–254 (1976)

    Google Scholar 

  • Corrodi, H., Fuxe, K., Hamberger, B., Ungerstedt, U.: ET495 and brain catecholamine mechanisms: Evidence for stimulation of dopamine receptor. Eur. J. Pharmacol. 20, 195–204 (1972)

    Google Scholar 

  • Corrodi, H., Fuxe, K., Hökfelt, T., Lidbrink, P., Ungerstedt, U.: Effect of ergot drugs on central catecholamine neurons: Evidence for stimulation of central dopamine neurons. J. Pharm. Pharmacol. 25, 409–412 (1973)

    Google Scholar 

  • Costall, B., Naylor, R. J.: The site and mode of action of ET495 for the mediation of stereotyped behaviour in the rat. Naunyn Schmiedebergs Arch. Pharmacol. 278, 117–133 (1973)

    Google Scholar 

  • DiChiara, G., Porceddu, M. L., Vargiu, L., Argiolas, A., Gessa, G. L.: Evidence for dopamine receptors in the mouse brain mediating sedation. Nature 264, 564–567 (1976)

    Google Scholar 

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

    Google Scholar 

  • Fuller, R. W., Perry, K. W.: Effect of lergotrile on 3,4-dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turn-over in rat brain. J. Neural Transm. 42, 23–35 (1978)

    Google Scholar 

  • Gessa, G. L., Vargiu, L., Crabai, F., Bocro, G. C., Caboni, F., Camba, R.: Selective increase of brain dopamine induced by γ-hydroxybutyrate. Life Sci. 5, 1921–1930 (1966)

    Google Scholar 

  • Gianutsos, G., Moore, K. E.: Increase in mouse brain dopamine content by baclofen: Effects of apomorphine and neuroleptics. Psychopharmacology 52, 217–221 (1977a)

    Google Scholar 

  • Gianutsos, G., Moore, K. E.: Dopaminergic supersensitivity in striatum and olfactory tubercle following chronic administration of haloperidol or clozapine. Life Sci. 20, 1585–1592 (1977b)

    Google Scholar 

  • Gianutsos, G., Moore, K. E.: Tolerance to the effects of baclofen and γ-butyrolactone on locomotor activity and dopaminergic neurons in the mouse. J. Pharmacol. Exp. Ther. 207, 859–869 (1978)

    Google Scholar 

  • Gianutsos, G., Thornburg, J. E., Moore, K. E.: Differential actions of dopamine agonists and antagonists on the γ-butyrolactoneinduced increase in mouse brain dopamine. Psychopharmacology 50, 225–229 (1976)

    Google Scholar 

  • Goldberg, L. I., Volkman, P. H., Kohli, J. D., Kotake, A. N.: Similarities and differences of dopamine receptors in the renal vascular bed and elsewhere. Adv. Biochem. Psychopharmacol. 16, 251–256 (1977)

    Google Scholar 

  • Goldstein, M., Lieberman, A., Battista, A. F., Lew, J. Y., Hata, F.: Bromocriptine, lergotrile: the antiparkinsonian efficacy and the interaction with monoaminergic receptors. Pharmacology [Suppl.] 16, 143–149 (1978)

    Google Scholar 

  • Grabowska, M., Antikiewicz, L., Maj, J., Michaluk, J.: Apomorphine and central serotonin neurons. Pol. J. Pharmacol. Pharm. 25, 29–39 (1976)

    Google Scholar 

  • Gudelsky, G. A., Moore, K. E.: Differential drug effects on dopamine concentrations and the rates of dopamine turnover in the median eminence, olfactory tubercle and corpus striatum. J. Neural Transm. 38, 95–105 (1976)

    Google Scholar 

  • Kebabian, J. W.: Multiple classes of dopamine receptors in mammalina central nervous system: the involvement of dopaminesensitive adenyl cyclase. Life Sci 23, 479–484 (1978)

    Google Scholar 

  • Kelly, P. H., Moore, K. E.: Dopamine concentrations in the rat brain following injections into the substantia nigra of baclofen, γ-amino butyric acid, γ-hydroxybutyric acid, apomorphine and amphetamine. Neuropharmacology 17, 169–174 (1978)

    Google Scholar 

  • Moore, K. E., Phillipson, O. T.: Effects of dexamethasone on phenylethanolamine-N-metyhl transferase and adrenaline in the brains and superior cervical ganglia of adult and neonatal rats. J. Neurochem. 25, 289–294 (1975)

    Google Scholar 

  • Moore, K. E., Thornburg, J. E.: Drug induced dopaminergic supersensitivity. Adv. Neurol. 9, 93–104 (1975)

    Google Scholar 

  • Mueller, G. P., Simpkins, J., Meites, J., Moore, K. E.: Differential effects of dopamine agonists and haloperidol on release of prolactin, thyroid stimulating hormone, growth hormone and luteinizing hormone in rats. Neuroendocrinology 20, 121–125 (1976)

    Google Scholar 

  • Persson, T., Waldeck, B.: Further studies on the possible interaction between dopamine and noradrenaline containing neurons in the brain. Eur. J. Pharmacol. 11, 315–320 (1970)

    Google Scholar 

  • Pijnenberg, A. J. J., Honig, W. M. M., van der Hayden, J. A. M., van Rossum, J. M.: Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. Eur. J. Pharmacol. 35, 45–58 (1976)

    Google Scholar 

  • Roth, R. H., Walters, J. R., Murrin, L. C., Morgenroth, V. H.: Dopamine neurons: Role of impulse flow and presynaptic receptors in the regulation of tyrosine hydroxylase. In: Pre-and postsynaptic receptors, E. Usdin, W. E. Bunney, eds., pp. 5–48. New York: Marcel Dekker 1975

    Google Scholar 

  • Snider, S. R., Hutt, C., Stein, B., Prasad, A. L. N., Fahn, S.: Correlation of behavioral inhibition or excitation produced by bromocriptine with changes in brain catecholamine turnover. J. Pharm. Pharmacol. 28, 563–566 (1976)

    Google Scholar 

  • Stutz, P. L., Stadler, P. A., Vigouret, J. M., Jaton, A.: Ergot alkaloids, new ergolines as selective dopaminergic stimulants. J. Med. Chem. 21, 754–757 (1978)

    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 

  • Thornburg, J. E., Moore, K. E.: A comparison of effects of apomorphine and ET495 on locomotor activity and circling behaviour in mice. Neuropharmacology 13, 189–197 (1974)

    Google Scholar 

  • Tye, N. C., Horsman, L., Wright, F. C., Large, B. T., Pullar, I. A.: Two dopamine receptors: supportive evidence with the rat rotational model. Eur. J. Pharmacol. 45, 87–90 (1977)

    Google Scholar 

  • Ungerstedt, U.: Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol. Scand. [Suppl.] 82, 69–93 (1971)

    Google Scholar 

  • Vigouret, J. M., Burki, H. R., Jaton, A. L., Zuger, P. E., Loew, D. M.: Neurochemical and neuropharmacological investigations with four ergot derivatives: bromocriptine, dihydroxyergotoxine, CF 25–397 and CM 29–712. Pharmacology [Suppl.] 16, 156–173 (1978)

    Google Scholar 

  • Walters, J. R., Roth, R. H., Aghajanian, G. K.: Dopaminergic neurons: similar biochemical and histochemical effects of γ-hydroxybutyrate and acute lesions of the nigro-striatal pathway. J. Pharmacol. Exp. Ther. 186, 630–639 (1973)

    Google Scholar 

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

    Google Scholar 

Download references

Author information

Author notes

  1. G. Gianutsos

    Present address: School of Pharmacy, The University of Connecticut, 06268, Storrs, CT, USA

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Michigan State University, 48824, East Lansing, MI, USA

    G. Gianutsos & K. E. Moore

Authors
  1. G. Gianutsos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. E. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gianutsos, G., Moore, K.E. Differential behavioral and biochemical effects of four dopaminergic agonists. Psychopharmacology 68, 139–146 (1980). https://doi.org/10.1007/BF00432131

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00432131

Key words

Search

Navigation