Skip to main content
Log in

Antagonism of morphine-induced central stimulation in mice by small doses of catecholamine-receptor agonists

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

Summary

The morphine (75 mg/kg i.p.) induced stimulation of motor activity in mice was significantly suppressed by small doses of central catecholamine (CA) receptor agonists, apomorphine (0.2 mg/kg) and clonidine (0.05 mg/kg). In the same dose, and at the same time interval as the behavioural stimulation was obtained, morphine did not significantly affect thein vivo rate of tyrosine hydroxylation in two dopamine (DA)-rich mouse brain regions, the corpus striatum and the limbic system, or in the noradrenaline (NA)-rich, but DA-poor hemispheres, measured as the Dopa-accumulation during 30 min after inhibition of aromatic amino-acid decarboxylase by 3-hydroxybenzylhydrazine (NSD 1015) 150 mg/kg. The apomorphine induced reduction in Dopa accumulation in the DA-rich brain regions was not significantly affected by morphine. The disappearance rate of brain NA after inhibition of tyrosine hydroxylase byα-methyltyrosine methylester (250 mg/kg), the utilization of NA, was accelerated by morphine, whereas that of DA was not affected. Clonidine (0.05 mg/kg) retarded selectively brain NA utilization, and also suppressed the morphine-induced increase in NA utilization.

In conclusion, morphine's stimulation of motor activity in mice, an effect which previously has been found to be correlated with its dependence producing action, could be inhibited by apomorphine or clonidine in small doses which inhibit brain DA- and NA-neurons, respectively. Thus, we have now shown the psychomotor stimulation by two euphoriant and dependenceproducing drugs, ethanol and morphine, to be suppressed by CA “autoreceptor” activation.

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

  • Agbajanian, G. K., Bunney, B. S. Dopamine “autoreceptors”: Pharmacological characterization by microiontophoretic single cell recording studies. Naunyn-Schmiedeberg's Arch. Pharmacol.297, 1–7 (1977).

    Google Scholar 

  • Ahlenlus, S., Carlsson, A., Engel, J., Svensson, T. H., Södersten, P. Antagonism byα-ethyltyrosine of the ethanol-induced stimulation and euphoria in man. Clin. Pharmacol. Ther.14, 586–591 (1973).

    Google Scholar 

  • Andén, N.-E., Corrodi, H., Fuxe, K. Turnover studies using synthesis inhibition. In: Metabolism of Amines in the Brain (Hooper, G., ed.), pp. 38–47. London: MacMillan. 1969.

    Google Scholar 

  • Andén, N.-E., Corrodi, H., Fuxe, K., Hökfelt, B., Hökfelt, T., Rydin, C., Svensson, T. H. Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci.9, 513–523 (1970).

    Google Scholar 

  • Andén, N.-E., Grabowska, M. Synthesis and disappearance of central noradrenaline and dopamine: Regulation via nerve impulses and receptor activity. In: Chemical Tools in Catecholamine Research, part II. Regulation of Catecholamines Turnover (Almgren, O., Carlsson, A., Engel, J., eds.). Amsterdam: North Holland Publishing Co. 1975.

    Google Scholar 

  • Andén, N.-E., Grabowska, M., Strömbom, U. Differentα-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn-Schmiedeberg's Arch. Pharmacol.292, 43–52 (1976).

    Google Scholar 

  • Andén, N.-E., Strömbom, U., Svensson, T. H. Dopamine and noradrenaline receptor stimulation: Reversal of reserpine-induced suppression of motor activity. Psychopharmacologia (Berl.)29, 289–298 (1973).

    Google Scholar 

  • Atack, C. V. The determination of dopamine by a modification of the dihydroxyindole fluorimetric assay. Brit. J. Pharmacol.48, 267–284 (1973).

    Google Scholar 

  • Atack, C. V., Magnusson, T. Individual elution of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from a single, strong cation exchange column by means of mineral acidorganic solvent mixtures. J. Pharm. Pharmacol.22, 625–627 (1970).

    Google Scholar 

  • Bertler, Å., Carlsson, A., Rosengren, E. A method for the fluorimetric determination of adrenaline and noradrenaline in tissue. Acta physiol. scand.44, 273–292 (1958).

    Google Scholar 

  • Brase, D. H., Loh, H. H., Way, E. L. Comparison of the effects of morphine on locomotor activity, analgesia and primary and protracted physical dependence in six mouse strains. J. Pharmacol. exp. Ther.201, 368–374 (1977).

    Google Scholar 

  • Carlsson, A. Receptor-mediated control of dopamine metabolism. In: Pre-and Postsynaptic Receptors (Usdin, E., Bunney, W. E., eds.), pp. 49–65. New York: Marcel Dekker. 1975.

    Google Scholar 

  • Carlsson, A., Davis, J. N., Kehr, W., Lindqvist, M., Atack, C. Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brainin vivo using in inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedeberg's Arch. Pharmacol.275, 153–168 (1972).

    Google Scholar 

  • 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).

    Google Scholar 

  • Carlsson, A., Engel, J., Svensson, T. H. Inhibition of ethanol-induced excitation in mice and rats byα-methyl-p-tyrosine. Psychopharmacologia (Berl.)26, 307–312 (1972).

    Google Scholar 

  • Carlsson, A., Lindqvist, M. Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J. Pharm. Pharmacol.25, 437–440 (1973).

    Google Scholar 

  • Carlsson, A., Magnusson, T., Svensson, T. H., Waldeck, B. Effect of ethanol on the metabolism of brain catecholamines. Psychopharmacologia (Berl.)30, 27–36 (1973).

    Google Scholar 

  • Carrol, B. J., Sharp, P. T. Monoamine mediation of the morphine-induced activation of mice. Brit. J. Pharmac.46, 124–139 (1972).

    Google Scholar 

  • Eddy, N. B.: Morphine. Action on the nervous system. In: The Pharmacology of the Opium Alkaloids (Krueger, H., Eddy, N. B., Sumwalt, M., eds.), pp. 1–76. Washington: U.S. Public Health Service No. 165. 1941.

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

    Google Scholar 

  • Engström, G., Svensson, T. H., Waldeck, B. Thyroxine and brain catecholamines: Increased transmitter synthesis and increased receptor sensitivity. Brain Res.77, 471–483 (1974).

    Google Scholar 

  • Goldstein, A., Sheehan, P. Tolerance of opioid narcotics. I. Tolerance to the “running fit” caused by levorphanol in the mouse. J. Pharmacol. exp. Ther.169, 175–184 (1969).

    Google Scholar 

  • Gomes, C., Svensson, T. H., Trolin, G. Effects of morphine on central catecholamine turnover, blood pressure and heart rate in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol.294, 141–147 (1976).

    Google Scholar 

  • Gunne, L. M., Jonsson, J., Fuxe, K. Effects of morphine intoxication on brain catecholamine neurons. Europ. J. Pharmacol.5, 338–342 (1969).

    Google Scholar 

  • Hanson, L. C. F. Evidence that the central action of amphetamine is mediated via catecholamines. Psychopharmacologia (Berl.)9, 78–80 (1966).

    Google Scholar 

  • Hollinger, M. Effect of reserpine,α-methyl-p-tyrosine, p-chlorophenylalanine and pargyline on levorphanol-induced running activity in mice. Arch. int. Pharmacodyn.179, 419–424 (1969).

    Google Scholar 

  • Jönsson, L. E., Gunne, L. M., Änggård, E. Effect ofα-methyltyrosine in amphetamine-dependent subjects. Pharmacol. Clin.2, 27–29 (1969).

    Google Scholar 

  • Kehr, W., Carlsson, A., Lindqvist, M. A method for the determination of 3, 4-dihydroxyphenylalanine (Dopa) in brain. Naunyn-Schmiedeberg's Arch. Pharmacol.274, 273–280 (1972).

    Google Scholar 

  • Korf, J., Bunney, B. S., Aghajanian, G. K. Noradrenergic neurons: Morphine inhibition of spontaneous activity. European J. Pharmacol.25, 165–169 (1974).

    Google Scholar 

  • Kuschinsky, K., Hornykiewicz, O. Effects of morphine on striatal dopamine metabolism: Possible mechanism of its opposite effect on locomotor activity in rats and mice. European J. Pharmacol.26, 41–50 (1974).

    Google Scholar 

  • Maj, J., Sowinska, H., Kapturkiewics, Z., Sarnek, J. The effect of L-DOPA and (+)-amphetamine on the locomotor activity after pimozide and phenoxybenzamine. J. Pharm. Pharmac.24, 412–414 (1972).

    Google Scholar 

  • Marshall, I., Smith, C. B. Acute and chronic morphine treatment and the hydroxylation of (1-14C)-l-tyrosine in the mouse brain. Brit. J. Pharmacol.50, 428–430 (1974).

    Google Scholar 

  • Montel, H., Starke, K., Taube, H. D. Influence of morphine and naloxone on the release of noradrenaline from rat cerebellar cortex slices. Naunyn-Schmiedeberg's Arch. Pharmacol.288, 427–433 (1975).

    Google Scholar 

  • Pohorecky, L. A., Jaffe, L. S. Noradrenergic involvement in the acute effects of ethanol. Res. Commun. Chem. Path. Pharmacol.12, 433–447 (1975).

    Google Scholar 

  • Randrup, A., Munkvad, I. Role of catecholamines in the amphetamine excitatory response. Nature (Lond.)211, 540 (1966).

    Google Scholar 

  • Rolinski, Z., Scheel-Kriiger, J. The effect of dopamine and noradrenaline antagonists on amphetamine induced locomotor activity in mice and rats. Acta pharmacol. et toxicol.33, 385–399 (1973).

    Google Scholar 

  • Scheel-Kriiger, J., Golembioivska, K., Mogilnicka, E. Evidence for increased apomorphine-sensitive dopaminergic effects after acute treatment with morphine. Psychopharmacology53, 55–63 (1977).

    Google Scholar 

  • Shuster, H., Hannam, R., Boyle, W. A simple method for producing tolerance to dihydromorphinone in mice. J. Pharmacol. exp. Ther.140, 149–154 (1963).

    Google Scholar 

  • Smith, C. B., Sheldon, M. I., Bednarczyk, J. H., Villarreal, J. E. Morphineinduced increases in the incorporation of3H-tyrosine into14C-dopamine and14C-norepinephrine in the mouse brain: Antagonism by naloxone and tolerance. J. Pharmacol. exp. Ther.180, 547–557 (1972).

    Google Scholar 

  • Smith, C. B., Villarreal, J. E., Bednarczyk, J. H., Sheldon, M. I. Tolerance to morphine-induced increases in14C-catecholamine synthesis in mouse brain. Science (Washington)170, 1106–1108 (1970).

    Google Scholar 

  • Starke, K., Mantel, H. Involvement ofα-receptors in clonidine-induced inhibition of transmitter release from central monoamine neurons. Neuropharmacology12, 1073–1080 (1973).

    Google Scholar 

  • Strömbom, U.: On the functional role of pre- and postsynaptic catecholamine receptors in brain. Acta physiol. scand. Suppl.431 (1975).

  • Strömbom, U. Catecholamine receptor agonists: Effects on motor activity and rate of tyrosine hydroxylation in mouse brain. Naunyn-Schmiedeberg's Arch. Pharmacol.292, 167–196 (1976).

    Google Scholar 

  • Strömbom, U., Svensson, T. H., Carlsson, A. Antagonism of ethanol's central stimulation in mice by small doses of catecholamine-receptor agonists. Psychopharmacology51, 293–299 (1977).

    Google Scholar 

  • Svensson, T. H. The effect of inhibition of catecholamine synthesis on dexamphetamine induced central stimulation. European J. Pharmacol.12, 161–166 (1969). Erratum:13, 139–140 (1970).

    Google Scholar 

  • Svensson, T. H., Bunney, B. S., Agbahanian, G. K. Inhibition of both noradrenergic and serotonergic neurons in brain by theα-adrenergic agonist clonidine. Brain Res.92, 291–306 (1975).

    Google Scholar 

  • Svensson, T. H., Waldeck, B. Significance of acetaldehyde in ethanolinduced effects on catecholamine metabolism and motor activity in the mouse. Psychopharmacologia (Berl.)31, 229–238 (1973).

    Google Scholar 

  • Waldeck, B. Ethanol and coffeine: a complex interaction with respect to locomotor activity and central catecholamines. Psychopharmacologia (Berl.)36, 209–220 (1974).

    Google Scholar 

  • Vander Wende, C., Spoerlein, M. T., Luc, N. C. Studies on the role of dopaminergic systems in morphine-induced motor activity. Comparison with noradrenergic and cholinergic systems. Res. Commun. Chem. Pathol. Pharmacol.11, 79–88 (1975).

    Google Scholar 

  • Weissman, A., Koe, B. K., Tenen, S. Antiamphetamine effects following inhibition of tyrosine hydroxylase. J. Pharmacol. exp. Ther.151, 339 to 352 (1966).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Strömbom, U., Svensson, T.H. Antagonism of morphine-induced central stimulation in mice by small doses of catecholamine-receptor agonists. J. Neural Transmission 42, 169–179 (1978). https://doi.org/10.1007/BF01675308

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01675308

Keywords

Navigation