Clonidine-induced locomotor hyperactivity in rats. The role of central postsynaptic alpha-adrenoceptors.
The alpha-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 alpha-methyl-p-tyrosine, or with reserpine plus low doses of yohimbine. The aplha-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 spiroperiodol, exert no antagonistic effect. The results indicate that in the brain of normal animals, clonidine predominantly activates presynaptic alpha-adrenoceptors on noradrenergic neurones and thereby induces sedation. After destruction of the noradrenergic fibres by 6-hydroxydopamine plus reserpine, activation of postsynaptic alpha-adrenoceptors prevails so that hyperactivity results.
D018663:Adrenergic Agents / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004347:Drug Interactions; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D018663:Adrenergic Agents; D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D008781:Methyltyrosines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine; D010134:Fenclonine