Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 297, Issue 3, pp 227–231 | Cite as

Clonidine-induced locomotor hyperactivity in rats

The role of central postsynaptic α-adrenoceptors
  • I. Żebrowska-Łupina
  • E. Przegaliński
  • M. Słoniec
  • Z. Kleinrok
Article

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.

Key words

Clonidine 6-Hydroxydopamine Reserpine Locomotor activity α-Adrenoceptors Brain Rats 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. Costall, B., Naylor, R. J.: On the mode of action of apomorphine. Europ. J. Pharmacol. 21, 350–361 (1973)Google Scholar
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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 1974Google Scholar
  17. Mabry, P. D., Campbell, B. A.: Serotoninergic inhibition of catecholamine-induced behavioural arousal. Brain Res. 49, 381–391 (1973)Google Scholar
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. Starke, K., Altmann, K. P.: Inhibition of adrenergic neurotransmission by clonidine: An action on prejunctional α-receptors. Neuropharmacology 12, 339–347 (1973)Google Scholar
  24. 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
  25. Starke, K., Borowski, E., Endo, T.: Preferential blockade of presynaptic α-adrenoceptors by yohimbine. Europ. J. Pharmacol. 34, 385–388 (1975)Google Scholar
  26. Strömbom, U.: Effects of low doses of catecholamine receptor agonists on exploration in mice. J. Neural Transm. 37, 229–235 (1975)Google Scholar
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. Żebrowska-Łupina, I., Kleinrok, Z.: Behavioural effects of yohimbine administered intraventricularly in the rat. Psychopharmacologic (Berl.) 33, 267–275 (1973)Google Scholar
  35. 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

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • I. Żebrowska-Łupina
    • 1
  • E. Przegaliński
    • 1
  • M. Słoniec
    • 1
  • Z. Kleinrok
    • 1
  1. 1.Department of Pharmacology, Institute of Clinical PathologySchool of MedicineLublinPoland

Personalised recommendations