Abstract
Small doses of apomorphine (0.03–0.25 mg/kg i.p.) caused a dose-dependent suppression of the ethanol-induced (2.36 g/kg, 15% v/v, i.p.) locomotor stimulation in mice and higher doses (0.5–2 mg/kg i.p.) caused a delayed suppression. The delay increased with increased doses. Very small doses of clonidine (0.025 or 0.05 mg/kg i.p.), which per se did not or only slightly affect the activity of control mice, also markedly suppressed the ethanol-induced motor stimulation. Ethanol alone (2.36 g/kg i.p.) did not significantly affect the amount of Dopa accumulating in various mouse brain regions (limbic system, corpus striatum, hemispheres and brain stem) during 30 min following administration of 3-hydroxybenzylhydrazine (NSD 1015), an inhibitor of aromatic amino-acid decarboxylase. Both the hypothermia and the locomotor stimulation by ethanol were antagonized by NSD 1015. The reduction in Dopa accumulation induced by a small dose of apomorphine (0.25 mg/kg i.p.) in the dopamine-rich regions in the mouse brain was slightly enhanced by ethanol, whereas the clonidine-induced decrease in Dopa accumulation was, if anything, reduced.
In conclusion, ethanol's behavioural stimulant action in mice can be largely suppressed by apomorphine or clonidine, drugs which in the small doses used probably inhibit central catecholamine (CA) neurons.
Similar content being viewed by others
References
Aghajanian, G. K., Bunney, B. S.: Pre- and postsynaptic feedback mechanisms in central dopaminergic neurons: In: Frontiers in neurology and neuroscience research. Seeman and Browns, eds, Chapter 2. The University of Toronto Press 1974
Ahlenius, S., Brown, R., Engel, J., Svensson, T. H., Waldeck, B.: Antagonism by nialamide of the ethanol-induced locomotor stimulation in mice. J. Neural Transmission 35, 175–178 (1974)
Ahlenius, S., Carlsson, A., Engel, J., Svensson, T. H., Södersten, P.: Antagonism by alpha methyltyrosine of the ethanol-induced stimulation and euphoria in man. Clin. Pharmacol. Ther. 14, 586–591 (1973)
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)
Andén, N.-E., Grabowska, M., Strömbom, U.: Different alpha-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)
Andén, N.-E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967)
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)
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 acid-organic solvent mixtures. J. Pharm. Pharmacol. 22, 625–627 (1970)
Bolme, P., Corrodi, H., Fuxe, K., Hökfelt, T., Lidbrink, P., Goldstein, M.: Possible involvement of central adrenaline neurons in vasomotor and respiratory control. Studies with clonidine and its interactions with piperoxane and yohimbine. Europ. J. Pharmacol. 28, 89–94 (1974)
Carlsson, A.: Receptor-mediated control of dopamine metabolism. In: Pre- and postsynaptic receptors, Usdin and Bunney, eds. New York: Marcel Dekker 1975a
Carlsson, A.: Dopaminergic autoreceptors. In: Chemical tools in catecholamine research, vol. 2, Almgren, Carlsson, and Engel, eds. Amsterdam: North-Holland/American Elsevier 1975b
Carlsson, A., Davis, J. N., Kehr, W., Lindqvist, M., Atack, C.: Simultaneous measurement of tyrosine and tryptophan hydroylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 153–168 (1972a)
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)
Carlsson, A., Engel, J., Svensson, T. H.: Inhibition of ethanol-induced excitation in mice and rats by α-methyl-p-tyrosine. Psychopharmacologia (Berl.) 26, 307–312 (1972b)
Carlsson, A., Kehr, W., Lindqvist, M.: Agonist-antagonist interaction on dopamine receptors in brain, as reflected in the rates of tyrosine and tryptophan hydroxylation. In: Proceedings of the V international Parkinson symposium, Vienna, 1975 (in press, 1976)
Carlsson, A., Kehr, W., Lindqvist, M., Magnusson, T., Atack, C. V.: Regulation of monoamine metabolism in the central nervous system. Pharmacol. Rev. 24, no. 2 (1972c)
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)
Carlsson, A., Magnusson, T., Svensson, T. H., Waldeck, B.: Effect of ethanol on the metabolism of brain catecholamines. Psychopharmacologia (Berl.) 30, 27–36 (1973)
Corrodi, H., Fuxe, K., Hökfelt, T.: The effect of ethanol on the activity of the catecholamine neurons in the rat brain. J. Pharm. Pharmacol. 18, 821–823 (1966)
Engel, J., Strömbom, U., Svensson, T. H., Waldeck, B.: Suppression by α-methyltyrosine of the ethanol-induced locomotor stimulation: Partial reversal by l-Dopa. Psychopharmacologia (Berl.) 37, 275–279 (1974)
Engström, G., Svensson, T. H., Waldeck, B.: Thyroxine and brain catecholamines: Increased trasmitter synthesis and increased receptor sensitivity. Brain Res. 77, 471–483 (1974)
Ernst, A. M.: Mode of action of apomorphine and dexamphet-amine on gnawing compulsion in rats. Psychopharmacologia (Berl.) 10, 316–323 (1967)
Fuxe, K., Lidbrink, P., Hökfelt, T., Bolme, P., Goldstein, M.: Effects of piperoxane on sleep and waking in the rat. Evidence for increased waking by blocking inhibitory adrenaline receptors on the locus coeruleus. Acta physiol. scand. 91, 566–567 (1974)
Hanson, L. C. F.: Evidence that the central action of amphetamine is mediated via catecholamines. Psychopharmacologia (Berl.) 9, 78–80 (1966)
Hanson, L. C. F.: Evidence that the central action of (+)-amphet-amine is mediated via catecholamines. Psychopharmacologia (Berl.) 10, 289–291 (1967)
Jönsson, L. E., Gunne, L. M., Änggård, E.: Effect of α-methyltyrosine in amphetamine-dependent subjects. Pharmacol. Clin. 2, 27–29 (1969)
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 (1972a)
Kehr, W., Carlsson, A., Lindqvist, M., Magnusson, T., Atack, C. V.: Evidence for a receptor-mediated feed-back control of striatal tyrosine hydroxylase activity. J. Pharm. Pharmacol. 24, 744–747 (1972b)
Lindqvist, M., Kehr, W., Carlsson, A.: Effect of pentobarbitone and diethyl ether on the synthesis of monoamines in rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 263–277 (1974)
Pohorecky, L. A., Jaffe, L. S.: Noradrenergic involvement in the acute effects of ethanol. Res. Commun. Chem. Path. Pharmacol. 12, 433–447 (1975)
Randrup, A., Munkvad, J.: Role of catecholamines in the amphetamine excitatory response. Nature (Lond.) 211, 540 (1966)
Read, G. W., Cutting, W., Furst, A.: Comparison of excited phases after sedatives and tranquilizers. Psychopharmacologia (Berl.) 1, 346–350 (1960)
Reynolds, G. S., Sommers, P. van: Effects of ethyl alcohol on avoidance behaviour. Science 132, 42–43 (1960)
Starke, K., Montel, H.: Involvement of α-receptors in clonidine-induced inhibition of transmitter release from central monoamine neurones. Neuropharmacology 12, 1073–1080 (1973)
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)
Svensson, T. H., Bunney, B. S., Aghajanian, G. K.: Inhibition of both noradrenergic and serotonergic neurons in brain by the α-adrenergic agonist clonidine. Brain Res. 92, 291–306 (1975)
Svensson, T. H., Waldeck, B.: Significance of acetaldehyde in ethanol-induced effects on catecholamine metabolism and motor activity in the mouse. Psychopharmacologia (Berl.) 31, 229–238 (1973)
Waldeck, B.: Ethanol and coffeine: a complex interaction with respect to locomotor activity and central catecholamines. Psychopharmacologia (Berl.) 36, 209–220 (1974)
Weiss, B., Laties, B. G.: Effects of amphetamine, chlorpromazine, pentobarbital and ethanol on operated response duration. J. Pharmacol. exp. Ther. 144, 17–23 (1964)
Weissman, A., Koe, B. K., Tenen, S.: Antiamphetamine effects following inhibition of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 151, 339–352 (1966)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Strömbom, U., Svensson, T.H. & Carlsson, A. Antagonism of ethanol's central stimulation in mice by small doses of catecholamine-receptor agonists. Psychopharmacology 51, 293–299 (1977). https://doi.org/10.1007/BF00431639
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00431639