Skip to main content
Log in

Clonidine-induced sedation in rats: Evidence for mediation by postsynapticα 2-adrenoreceptors

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

Summary

The effect of low doses of clonidine on exploration and motility was investigated in rats after destruction of central noradrenergic systems by 6-hydroxydopamine (6-OHDA) or DSP-4. In accordance with previous results, clonidine decreased exploration and motility in control animals. This sedative effect of clonidine was potentiated in animals that suffered selective and extensive depletions of brain NA as a result of neonatal treatment with 6-OHDA. Depletion of NA by administration of DSP-4 to adult animals did not influence clonidine's sedative effects. Yohimbine, but not phentolamine, antagonized clonidine-induced hypomotility both in control and in neonatal 6-OHDA treated groups. The results suggest that clonidineinduced sedation is mediated by postsynapticα 2-adrenoreceptors.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Andén, N.-E., Corrodi, H., Fuxe, K., Hokfelt, B., Hokfelt, 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., Strombom, U.: Differentα-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn-Schmiedeberg's Arch. Pharmacol.293, 43–52 (1976).

    Google Scholar 

  • Angelletti, P. U.: Chemical sympathectomy in newborn animals. Neuropharmacology10, 55–59 (1971).

    PubMed  Google Scholar 

  • Bruner, H., Klein, K. E.: Experimentelle Untersuchungen über die Veränderungen der Psychomotorischen Leistungsbereitschaft unter dem Einfluss eines Antihypertonicums. In: Hochdrucktherapie (Heilmeyer, L., Holtmeier, H.-J., Pfeiffer, E. F., Hrsg.), S. 180–184. Stuttgart: G. Thieme. 1968.

    Google Scholar 

  • Cedarbaum, J. M., Agbajanian, 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. Eur. J. Pharm.44, 375–385 (1977).

    Google Scholar 

  • Clark, D. W. J., Laverty, R., Phelan, E. L.: Long-lasting peripheral and central effects of 6-hydroxydopamine in rats. Brit. J. Pharmac.44, 233–243 (1972).

    Google Scholar 

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

    PubMed  Google Scholar 

  • Drew, G. M., Gower, A. J., Marriott, A. S.:α 2-adrenoreceptors mediate clonidine-induced sedation in the rat. Brit. J. Pharmac.67, 133–141 (1979).

    Google Scholar 

  • Delini-Stula, A., Baumann, P., Buch, O.: Depression of exploratory activity by clonidine in rats as a model for the detection of relative pre- and post-synaptic central noradrenergic receptor selectivity ofα-adrenolytic drugs. Naunyn-Schmiedeberg's Arch. Pharmacol.307, 115–122 (1979).

    Google Scholar 

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

    Google Scholar 

  • Jaim-Etcheverry, G., Zieher, L. M.: DSP-4: a novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res.188, 513–523 (1980).

    PubMed  Google Scholar 

  • Kobinger, W.: Centralα-adrenergic system as targets for hypotensive drugs. Rev. Physiol. Biochem. Pharmacol.81, 39–100 (1978).

    PubMed  Google Scholar 

  • Langer, S. Z.: Presynaptic receptors and their role in the regulation of transmitter release. Sixth Gaddum Memorial Lecture. Br. J. Pharmacol.60, 481–497 (1977).

    PubMed  Google Scholar 

  • Langer, S. Z.: Presynaptic regulation of the release of catecholamines. Pharmac. Reviews32, 337–362 (1981).

    Google Scholar 

  • Langer, S. Z., Massingham, R.:α-adrenoreceptors and the clinical pharmacology of clonidine. Proc. World Conference on Clinical Pharmacology and Therapeutics (Turner, P., ed.), pp. 158–164. New York: Macmillan. 1980.

    Google Scholar 

  • Laverty, R., Taylor, K. M.: Behavioral and biochemical effects of 2-(2, 6-dichlorolophenylamino)-2-imidazoline hydrochloride (ST155) on the central nervous system. Br. J. Pharmac.35, 253–264 (1969).

    Google Scholar 

  • McGeer, E. G., McGeer, P. L.: Catecholamine content of the spinal cord. Can. J. Biochem.40, 1141–1151 (1962).

    Google Scholar 

  • Ross, S. B.: Long-term effect of N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurons in the rat brain and heart. Brit. J. Pharmacol.58, 521–527 (1976).

    Google Scholar 

  • Schmitt, H.: The pharmacology of clonidine and related products. In: Antihypertensive Agents (Gross, F., ed.), pp.299–378. Berlin-Heidelberg-New York: Springer. 1977.

    Google Scholar 

  • Skolnick, P., Daly, J. W., Segal, D. S.: Neurochemical and behavioral effects of clonidine and related imidazolines: Interaction with α-adrenoreceptors. Eur. J. Pharmacol.47, 451–455 (1978).

    PubMed  Google Scholar 

  • Starke, K.: Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol. Pharmacol.77, 1–124 (1977).

    Google Scholar 

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

    PubMed  Google Scholar 

  • Strombom, 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).

    Google Scholar 

  • Strombom, U., Svensson, T.: Clonidine: Attenuation of sedative action by facilitated central noradrenergic neurotransmission. J. Neural Transm.47, 29–39 (1980).

    PubMed  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 

  • Taylor, K. M., Clark, D. W. J., Laverty, R., Phelan, E. L.: Specific noradrenergic neurons destroyed by 6-hydroxydopamine injection into newborn rats. Nature New Biol.239, 247–248 (1972).

    PubMed  Google Scholar 

  • U'Prichard, D. C., Bechtel, W. P., Rouot, B. M., Snyder, S. H.: Multiple apparentα-noradrenergic receptor binding sites in rat brain. Effect of 6-hydroxydopamine. Mol. Pharmacol.16, 47–60 (1979).

    PubMed  Google Scholar 

  • U'Prichard, D. C., Reisine, T. D., Mason, S. T., Fibiger, H. C., Yamamura, H. I.: Modulation of rat brainα- andβ-adrenergic receptor population by lesion of the dorsal noradrenergic bundle. Brain Res.187, 143–154 (1980).

    PubMed  Google Scholar 

  • Van Zwieten, P. A.: Antihypertensive drugs with a central action. In: Progress in Pharmacology, pp. 1–63. Stuttgart: Gustav Fischer-Verlag. 1975.

    Google Scholar 

  • Westfall, T. C.: Local regulation of adrenergic neurotransmission. Physiol. Rev.57, 659–728 (1977).

    PubMed  Google Scholar 

  • Whishaw, I. Q., Cooper, R. M.: Strychnine and suppression of exploration. Physiol. Behav.5, 647–649 (1970).

    PubMed  Google Scholar 

  • Zebrowska-Lupina, L., Przegalinski, E., Sloniec, M., Kleinrok, Z.: Clonidine-induced hyperactivity in rats. The role of central postsynapticα-adrenoreceptors. Naunyn-Schmiedeberg's Arch. Pharmacol.297, 227–231 (1977).

    Google Scholar 

  • Zis, A. P., Fibiger, H. C.: Functional evidence for postsynaptic supersensitivity of central noradrenergic receptors after denervation. Nature256, 659–661 (1975).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spyraki, C., Fibiger, H.C. Clonidine-induced sedation in rats: Evidence for mediation by postsynapticα 2-adrenoreceptors. J. Neural Transmission 54, 153–163 (1982). https://doi.org/10.1007/BF01254925

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01254925

Key words

Navigation