Interference of clonidine and alpha-methyl-p-tyrosine with stress and central histaminergic stimulation of the corticosterone response in rats.

In conscious rats clonidine given intracerebroventricularly 1 h prior to a mild stress of immobilization intensified the stress-induced increase of pituitary-adrenocortical response, measured indirectly through corticosterone concentration in blood serum. The corticosterone response to clonidine was abolished by i.c.v. pretreatment of rats with yohimbine, an alpha 2-adrenergic antagonist, and was antagonized by pretreatment with phenoxybenzamine, an alpha 1-adrenergic antagonist. Clonidine intensified also the corticosterone response induced in stressed rats by i.c.v. injected histamine, 2-pyridylethylamine (PEA), a H1-receptor agonist, and dimaprit, a H2-receptor agonist. The depletion of brain catecholamines by alpha-methyl-p-tyrosine (alpha-MT) considerably increased the corticosterone response to stress but did not substantially change the response to histamine, PEA and dimaprit in stressed rats. These results suggest that clonidine increases the corticosterone secretion induced by a mild stress and histamine and histamine H1 and H2 agonists mainly through the activation of central alpha 2-adrenoceptors. The increase by alpha-MT of the stress-induced corticosterone response may indicate the inhibitory role of central catecholamines in the pituitary-adrenocortical response to stress in rats.