Original scientific paper
The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamicpituitary- adrenal axis activity in female rats
Dubravka Švob Štrac
; Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
Dorotea Muck-Šeler
; Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
Abstract
Aim 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 (α2-adrenoreceptor agonist),
yohimbine (α2-adrenoreceptor antagonist), alpha-methylp-
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 diazepaminduced
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.
Conclusion The results suggest that α2-adrenoreceptors
activity, as well as intact presynaptic noradrenergic function,
are required for the suppressive effect of diazepam on
the HPA axis activity.
Keywords
Hrčak ID:
84156
URI
Publication date:
15.6.2012.
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