The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamic-pituitary-adrenal axis activity in female rats.
OBJECTIVE
To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity.


METHODS
Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α(2)-adrenoreceptor agonist), yohimbine (α(2)-adrenoreceptor antagonist), alpha-methyl-p-tyrosine (α-MPT, an inhibitor of catecholamine synthesis), or reserpine (a catecholamine depleting drug) and yohimbine.


RESULTS
Diazepam administered in a dose of 2.0 mg/kg suppressed basal HPA axis activity, ie, decreased plasma corticosterone and ACTH levels. Pretreatment with clonidine or yohimbine failed to affect basal plasma corticosterone and ACTH concentrations, but abolished diazepam-induced inhibition of the HPA axis activity. Pretreatment with α-MPT, or with a combination of reserpine and yohimbine, increased plasma corticosterone and ACTH levels and prevented diazepam-induced inhibition of the HPA axis activity.


CONCLUSIONS
The results suggest that α(2)-adrenoreceptors activity, as well as intact presynaptic noradrenergic function, are required for the suppressive effect of diazepam on the HPA axis activity.
Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
Dubravka
D
Švob Štrac
Dorotea
D
Muck-Šeler
Nela
N
Pivac
D059331:Adrenergic Neurons / Q000187:drug effects*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D003975:Diazepam / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D015016:Yohimbine; D019805:alpha-Methyltyrosine; D012110:Reserpine; D000324:Adrenocorticotropic Hormone; D003000:Clonidine; D003975:Diazepam; D003345:Corticosterone