Effect of intracerebroventricular clonidine on serum corticosterone levels in rats.
In conscious, nonstressed rats clonidine given intracerebroventricularly (i.c.v.) increased the pituitary-adrenocortical response evaluated indirectly from corticosterone concentration. The maximum significant increase occurred 60 min after a dose of 10 micrograms. The alpha 2-adrenoceptor antagonist yohimbine given alone i.c.v. in low doses (0.05-1 microgram) had no effect on plasma corticosterone levels, but at higher doses (5 and 10 micrograms) it produced a significant rise in these levels. Phenoxybenzamine (0.05-10 micrograms, i.c.v.) caused a dose-related increase in corticosterone secretion. Pretreatment of rats with yohimbine considerably antagonized (up to 70%) the increase of corticosterone response induced by clonidine. Phenoxybenzamine failed to alter this effect. The depletion of brain catecholamines by alpha-methyl-p-tyrosine caused an increase in serum corticosterone concentration. The rise was suppressed by clonidine (10 micrograms, i.c.v.), and this suppression was antagonized in part by pretreatment with yohimbine. These data support the concept of the noradrenergic inhibition of ACTH secretion in rats. It seems likely that clonidine injected i.c.v. induces stimulation of corticosterone through the activation of presynaptic alpha 2-adrenoceptors and inhibition of noradrenaline release. The clonidine-induced inhibition of corticosterone after alpha-methyl-p-tyrosine seems to be mediated by alpha-adrenoceptors located postsynaptically.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D011942:Receptors, Adrenergic, alpha; D010643:Phenoxybenzamine; D015016:Yohimbine; D019805:alpha-Methyltyrosine; D000324:Adrenocorticotropic Hormone; D003000:Clonidine; D003345:Corticosterone