Skip to main content
SpringerLink
Log in

Clonidine-induced locomotor hyperactivity in rats

The role of central postsynaptic α-adrenoceptors

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The α-adrenergic agonist, clonidine, causes sedation in normal rats. The present study demonstrates that clonidine evokes strong locomotor stimulation in rats pretreated with 6-hydroxydopamine plus reserpine. Similar, but less intensive hyperactivity is observed in rats given clonidine after combined pretreatment with 6-hydroxydopamine plus p-chlorophenylalanine plus α-methyl-p-tyrosine, or with reserpine plus low doses of yohimbine. The α-adrenolytic drugs, phenoxybenzamine, phentolamine and aceperone, as well as high doses of yohimbine, antagonise the clonidine-induced locomotor stimulation; in contrast, the dopamine receptor blocking agents, pimozide and spiroperidol, exert no antagonistic effect. The results indicate that in the brain of normal animals, clonidine predominantly activates presynaptic α-adrenoceptors on noradrenergic neurones and thereby induces sedation. After destruction of the noradrenergic fibres by 6-hydroxydopamine plus reserpine, activation of postsynaptic α-adrenoceptors prevails so that hyperactivity results.

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

    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 

  • Andén, N. E., Grabowska, M., Strömbom, U.: Different alphaadrenoreceptors 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 

  • Breese, G. R., Traylor, T. D.: Effect of 6-hydroxydopamine on brain norepinephrine and dopamine: Evidence for selective degeneration of catecholoamine neurons. J. Pharmacol. exp. Ther. 174, 413–420 (1970)

    Google Scholar 

  • Breese, G. R., Cooper, B. R., Mueller, R. A.: Evidence for involvement of 5-hydroxytryptamine in the actions of amphetamine. Brit. J. Pharmacol. 52, 307–314 (1974)

    Google Scholar 

  • Connon, E., Wyatt, R. J., Gillin, J. C.: Potentiation of amphetamine-induced hyperactivity by acute but not chronic parachlorophenylalanine treatment in the rat. Life Sci. 18, 763–768 (1976)

    Google Scholar 

  • Corrodi, H., Fuxe, K., Kjungdahl, A., Ögren, S. O.: Studies on the action of some psychoactive drugs on central noradrenaline neurones after inhibition of dopamine-β-hydroxylase. Brain Res. 24, 451–470 (1970)

    Google Scholar 

  • Costall, B., Naylor, R. J.: On the mode of action of apomorphine. Europ. J. Pharmacol. 21, 350–361 (1973)

    Google Scholar 

  • Delbarre, B., Schmitt, H.: Sedative effects of α-sympathomimetic drugs and their antagonism by adrenergic and cholinergic blocking drugs. Europ. J. Pharmacol. 13, 356–363 (1971)

    Google Scholar 

  • Delbarre, B., Schmitt, H.: A further attempt to characterize sedative receptors activated by clonidine in chickens and mice. Europ. J. Pharmacol. 22, 355–359 (1973)

    Google Scholar 

  • Dunstan, R., Jackson, D. M.: The demonstration of a change in adrenergic receptor sensitivity in the central nervous system of mice after withdrawal from long-term treatment with haloperidol. Psychopharmacology 48, 105–114 (1976)

    Google Scholar 

  • Finch, L., Buckingham, R. E., Moore, R. A., Bucher, T. J.: Evidence for a central α-sympathomimetic action of clonidine in the rat. J. Pharm. Pharmacol. 27, 181–186 (1975)

    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. Neuopharmacology 14, 707–714 (1975)

    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. Brit. J. Pharmacol. 35, 253–264 (1969)

    Google Scholar 

  • Lloyd, K. G., Bartholini, G.: The effect of methiothepin on cerebral monoamine neurons. In: Serotonin — New vistas, histochemistry and pharmacology, advances in biochemical psychopharmacology, vol. 10 (E. Costa, G. L. Gessa, and M. Sandler, eds.), pp. 305–309. New York: Raven Press 1974

    Google Scholar 

  • Mabry, P. D., Campbell, B. A.: Serotoninergic inhibition of catecholamine-induced behavioural arousal. Brain Res. 49, 381–391 (1973)

    Google Scholar 

  • Maj, J., Grabowska, M., Mogilnicka, E.: The effect of l-DOPA on brain catecholamines and motility in rats. Psychopharmacologia (Berl.) 22, 162–171 (1971)

    Google Scholar 

  • Maj, J., Sowińska, H., Baran, L., Kapturkiewicz, Z.: The effect of clonidine on locomotor activity in mice. Life Sci. 11, 483–491 (1972)

    Google Scholar 

  • Maj, J., Baran, L., Grabowska, M., Sowińska, H.: Effect of clonidine on the 5-hydroxytryptamine and 5-hydroxyindoleacetic acid brain levels. Biochem. Pharmacol. 22, 2679–2683 (1973)

    Google Scholar 

  • Malec, D., Langwiński, R., Kruszewska, A.: The role of serotonin in ephedrine-induced stereotypy and hypermotility. Arch. Immunol. Ter. exp. (Wroclaw) 24, 829–836 (1976)

    Google Scholar 

  • Scheel-Krüger, J.: Studies of various amphetamines, apomorphine and clonidine on body temperature and brain 5-hydroxytryptamine metabolism in rats. Psychopharmacologia (Berl.) 36, 189–202 (1974)

    Google Scholar 

  • Starke, K., Altmann, K. P.: Inhibition of adrenergic neurotransmission by clonidine: An action on prejunctional α-receptors. Neuropharmacology 12, 339–347 (1973)

    Google Scholar 

  • Starke, K., Montel, H.: Involvement of α-receptors in clonidine-induced inhibition of transmitter release from central monoamine neurones. Neuropharmacology 12, 1073–1080 (1973)

    Google Scholar 

  • Starke, K., Borowski, E., Endo, T.: Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Europ. J. Pharmacol. 34, 385–388 (1975)

    Google Scholar 

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

    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)

    Google Scholar 

  • Svensson, T., Waldeck, B.: On the role of brain catecholamines in motor activity: Experiments with inhibitors of synthesis and of monoamine oxidase. Psychopharmacologia (Berl.) 18, 357–365 (1970)

    Google Scholar 

  • 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)

    Google Scholar 

  • Thornburg, J. E., Moore, K. E.: Supersensitivity to dopamine agonists following unilateral, 6-hydroxydopamine-induced striatal lesions in mice. J. Pharmacol. exp. Ther. 192, 42–49 (1975)

    Google Scholar 

  • Ungerstedt, U.: Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta physiol. scand., Suppl. 367, 69–93 (1971)

    Google Scholar 

  • Uretsky, N., Iversen, L. L.: Effects of 6-hydroxydopamine on catecholamine containing neurones in the rat brain. J. Neurochem. 17, 269–278 (1970)

    Google Scholar 

  • Żebrowska-Łupina, I.: The effect of nordrenergic receptor blocking agents on 5-hydroxytryptamine turnover in the brain of rats. Pol. J. Pharmacol. Pharm. 28, 341–347 (1976)

    Google Scholar 

  • Żebrowska-Łupina, I., Kleinrok, Z.: Behavioural effects of yohimbine administered intraventricularly in the rat. Psychopharmacologic (Berl.) 33, 267–275 (1973)

    Google Scholar 

  • Żebrowska-Łupina, I., Kleinrok, Z.: The effect of α-adrenolytics on the levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in rat's brain. Pol. J. Pharmacol. Pharm., Suppl. 27, 241–245 (1975)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Institute of Clinical Pathology, School of Medicine, PL-20-090, Lublin, Poland

    I. Żebrowska-Łupina, E. Przegaliński, M. Słoniec & Z. Kleinrok

Authors
  1. I. Żebrowska-Łupina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Przegaliński
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Słoniec
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Z. Kleinrok
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This study was supported by Polish Academy of Sciences (10.4). Preliminary accounts were presented at the Pharmacology Meeting, Hannover, September 14–17, 1976 and at the 1 st Joint Symposium of Hungarian and Polish Pharmacological Societies, Zakopane, October, 13–15, 1976

Rights and permissions

Reprints and permissions

About this article

Cite this article

Żebrowska-Łupina, I., Przegaliński, E., Słoniec, M. et al. Clonidine-induced locomotor hyperactivity in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 227–231 (1977). https://doi.org/10.1007/BF00509265

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00509265

Key words

Search

Navigation