Skip to main content
SpringerLink
Log in

Clonidine: Attenuation of sedative action by facilitated central noradrenergic neurotransmission

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

Summary

Administration of clonidine, 0.05 mg/kg i.p. to mice 30 min before trial significantly depressed the exploration of a Y-maze. This effect was completely antagonized by l-amphetamine, 0.75 mg/kg i.p., given 10 min before trial, which by itself did not change the behaviour studied. The clonidine-induced behavioural depression also appeared reduced after pre-treatment with desipramine (10 mg/kg i.p., 30 min before clonidine) which, like l-amphetamine, by itself was inactive. The above treatment with clonidine significantly reduced the accumulation of dopa after inhibition of central aromatic L-aminp acid decarboxylase both in the noradrenaline (NA) rich neocortex and the dopamine-rich corpus striatum, whereas the dopa accumulation in the limbic brain regions was not significantly affected. l-Amphetamine, 0.75 mg/kg i.p., did not by itself significantly affect the dopa accumulation, but reduced the clonidine-induced effects. The results are compatible with the notion that the depression of exploratory behaviour by clonidine is related to impaired central NA-neurotransmission and rule out the possibility that it is due to activation of central post-synaptic NA-(α-)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., Corrodi, H., Fuxe, K., Hökfelt, B., Hökfelt, T., Rydin, C., Svensson, T. Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci.9, 513–523 (1970).

    PubMed  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. Adrenergic receptor blocking agents: Effects on central noradrenaline and dopamine receptors and on motor activity. Psychopharmacologia (Berl.)38, 91–103 (1974).

    Google Scholar 

  • Andén, N.-E., Strömbom, U., Svensson, T. H. Dopamine and noradrenaline receptor stimulation. Reversal of reserpine-induced suppression of motor activity. Psychopharmacologia29, 289–298 (1973).

    PubMed  Google Scholar 

  • Andén, N.-E., Strömbom, U., Svensson, T. H. Locomotor stimulation by L-dopa: Relative importance of noradrenaline receptor activation. Psychopharmacology54, 243–248 (1977).

    PubMed  Google Scholar 

  • Bacq, Z. M., Fredericq, H. Action adrenolytique d'un dérive du dioxane (933 F). C. R. Soc. Biol. (Paris)116, 806–808 (1934).

    Google Scholar 

  • 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. European J. Pharmacol.28, 89–94 (1974).

    Google Scholar 

  • Braestrup, C. Effects of phenoxybenzamine, aceperone and clonidine on the level of 3-methoxy-4-hydroxyphenylglycol (MOPEG) in rat brain. J. Pharm. Pharmacol.26, 139–141 (1974).

    PubMed  Google Scholar 

  • Briant, R. H., Reid, J. L., Dollery, C. T. Interaction between clonidine and desipramine in man. Brit. med. J.1, 522–523 (1973).

    PubMed  Google Scholar 

  • Bunney, B. S., Walters, J. R., Kuhar, M. J., Roth, R. H., Aghajanian, G. K. D- and L-amphetamine stereoisomers: Comparative potencies in affecting the firing of central dopaminergic and noradrenergic neurons. Psychopharmacology Communications1, 177–190 (1975).

    PubMed  Google Scholar 

  • Carlsson, A. Effect of drugs on amine uptake mechanisms in the brain. In: Bayer Symposium II on New Aspects of Storage and Release Mechanisms of Catecholamines (Schumann, H. J., Kroneberg, G., eds.), pp. 223–233. Berlin-Heidelberg-New York: Springer. 1970.

    Google Scholar 

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

    PubMed  Google Scholar 

  • Cedarbaum, J. M., Aghajanian, G. K. Noradrenergic neurons of the locus coeruleus: inhibition by epinephrine and activation by theα-antagonist piperoxane. Brain Res.112, 413–419 (1976).

    PubMed  Google Scholar 

  • Cedarbaum, J. M., Aghajanian, G. K. Catecholamine receptors on locus coeruleus neurons: pharmacological characterization. Europ. J. Pharmacol.44, 375–385 (1977).

    Google Scholar 

  • Chiara, G. D., Porceddu, W. L., Vargiu, L., Argiolos, A., Gessa, G. L. Evidence for dopamine receptors mediating sedation in the mouse brain. Nature264, 564–566 (1976).

    PubMed  Google Scholar 

  • Davis, M., Cedarbaum, J. M., Aghajanian, G. K., Gendelman, D. S. Effects of clonidine on habutation and sensitization of acoustic startle in normal, decerebrate and locus coeruleus lesioned rats. Psychopharmacology51, 243–253 (1977).

    PubMed  Google Scholar 

  • De Vleeschbouver, G. Au sujet de l'action due diéthylaminomethyl-3-benzodioxane (F 833) et de piperiméthyl-3-benzodioxane (F 933) sur le système circulatoire. Arch. Int. Pharmacodyn.50, 251–295 (1935).

    Google Scholar 

  • Farnebo, L.-O., Hamberger, B. Drug-induced changes in the release of3H-monoamines from field stimulated rat brain slices. Acta physiol. scand. Suppl.371, 35–44 (1971).

    PubMed  Google Scholar 

  • Ferris, R. M., Tane, F. L. M., Maxwell, R. H. A comparison of isomers of amphetamine, deoxypyrrodol and methylphenidate to inhibit the uptake of tritiated catecholamines into rat cerebral cortex slices, synaptosomal preparations of rat cerebral cortex, hypothalamus and striatum and into adrenergic nerves of rabbit cortex. J. Pharmacol. exp. Ther.181, 407 to 416 (1972).

    Google Scholar 

  • Florio, V., Bianchi, L., Longo, V. G. A study of the central effects of sympathomimetic drugs: EEG and behavioural investigations on clonidine and naphazoline. Neuropharmacology14, 707–714 (1975).

    PubMed  Google Scholar 

  • Harris, J. E., Baldessarini, R. J. Uptake of (3H)-catecholamines by homogenates of rat corpus striatum and cerebral cortex, effects of amphetamine analogues. Neuropharmacol.12, 669–679 (1973).

    Google Scholar 

  • Häusler, G. Clonidine-induced inhibition of sympathetic nerve activity: No indication for a central presynaptic or an indirect sympathomimetic mode of action. Naunyn-Schmiedeberg's Arch. Pharmacol.286, 97–111 (1974).

    Google Scholar 

  • Hökfelt, T., Fuxe, K., Goldstein, M., Johansson, O. Immunohistochemical evidence for the existence of adrenaline neurons in the rat brain. Brain Res.66, 235–251 (1974).

    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 

  • Kobinger, W., Pichier, L. The central modulatory effect of clonidine on the cardiodepressor reflex after suppression of synthesis and storage of noradrenaline. European J. Pharmacol.30, 56–62 (1975).

    Google Scholar 

  • Kobinger, W., Pichier, L. Centrally induced reduction in sympathetic tone-a postsynapticα-adrenoceptor-stimulating action of imidazolines. European J. Pharmacol.40, 311–320 (1976).

    Google Scholar 

  • Laverty, R., Taylor, K. M. Behavioural and biochemical effects of 2-(2, 6-dichlorophenylamino)-2-imidazoline hydrochloride (ST 155) on the central nervous system. Br. J. Pharmac.35, 253–264 (1969).

    Google Scholar 

  • Maj, J., Grabowska, M., Gajda, L. Effect of apomorphine on motility in rats. European J. Pharmacol.17, 208–214 (1972).

    Google Scholar 

  • Nybäck, H. V., Walters, J. R., Aghajanian, G. K., Roth, R. H. Tricyclic antidepressants: Effect on the firing rate of brain noradrenergic neurons. European J. Pharmacol.32, 302–312 (1975).

    Google Scholar 

  • Rochelte, L., Bralet, A. M., Bralet, J. Influence de la clonidine et la libération de la noradrenaline dans différentes structures cérébrales du rat. J. Pharmacol. (Paris)5, 209–220 (1974).

    Google Scholar 

  • Skolnick, P., Daly, J. W., Segal, D. S. Neurochemical and behavioural effects of clonidine and related imidazolines: Interaction withα-adrenoceptors. European J. Pharmacol.47, 451–455 (1978).

    Google Scholar 

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

    PubMed  Google Scholar 

  • Strömbom, U. Effects of low doses of catecholamine receptor agonists on exploration in mice. J. Neural Transm.37, 229–235 (1975).

    PubMed  Google Scholar 

  • Strömbom, U. Catecholamine receptor agonists: Effects on motor activity and rate of tyrosine hydroxylation in mouse brain. Naunyn-Schmiedeberg's Arch. Pharmacol.292, 167–176 (1976 a).

    Google Scholar 

  • Strömbom, U.: On the functional role of pre- and postsynaptic catecholamine receptors in brain. Thesis, December 1975, Göteborg. Arch, physiol. scand. Suppl.431 (1976 b).

  • Strömbom, U. Antagonism by haloperidol of locomotor depression induced by small doses of apomorphine. J. Neural Transm.40, 191–194 (1977).

    PubMed  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).

    PubMed  Google Scholar 

  • Svensson, T. H. On the role of central noradrenaline in the regulation of motor activity and body temperature in the mouse. Naunyn-Schmiedeberg's Arch. Pharmacol.271, 111–120 (1971 a).

    Google Scholar 

  • Svensson, T. H. Functional and biochemical effects of d- and l-amphetamine on central catecholamine neurons. Naunyn-Schmiedeberg's Arch. Pharmacol.271, 170–180 (1971 b).

    Google Scholar 

  • Svensson, T. H. Centralα-adrenoceptors and affective symptoms and disorder. In: Depressive Disorders (13th Symposium Medicum Hoechst). Stuttgart-New York: F. K. Schattauer. 1978.

    Google Scholar 

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

    PubMed  Google Scholar 

  • Svensson, T. H., Strömbom, U. Discontinuation of chronic clonidine treatments: Evidence for facilitated brain noradrenergic neurotransmission. Naunyn-Schmiedeberg's Arch. Pharmacol.299, 83–87 (1977).

    Google Scholar 

  • Svensson, T. H., Usdin, T.: Brain noradrenergic neurons: Feedback inhibition after acute and chronic treatment with tricyclic antidepressants. Abstract. 4th International Catecholamine Symposium, Pacific Grove, California (1978).

  • Svensson, T. H., Waldeck, B. On the significance of central noradrenaline for motor activity: Experiments with a new dopamine-β-hydroxylase inhibitor. European J. Pharmacol.7, 278–282 (1969).

    Google Scholar 

  • Tbornburg, J. E., Moore, K. E. Dopamine and norepinephrine uptake by rat brain synaptosomes: relative inhibitory potencies of l- and d-amphetamine and amantadine. Res. Comm. Chem. Path. Pharmacol.5, 81–89 (1973).

    Google Scholar 

  • Zebrowska-Lupina, I., Przégalinski, E., Sloniec, M., Kleinrok, Z. Clonidine-induced locomotor hyperactivity in rats. Naunyn-Schmiedeberg's Arch. Pharmacol.297, 227–231 (1977).

    Google Scholar 

Download references

Author information

Author notes

  1. T. H. Svensson

    Present address: Department of Pharmacology, University of Göteborg, Sweden

Authors and Affiliations

  1. Department of Pharmacology, University of Göteborg, Sweden

    U. Strömbom

Authors
  1. U. Strömbom
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. H. Svensson
    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

Strömbom, U., Svensson, T.H. Clonidine: Attenuation of sedative action by facilitated central noradrenergic neurotransmission. J. Neural Transmission 47, 29–39 (1980). https://doi.org/10.1007/BF01256637

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01256637

Key words

Search

Navigation