INVOLVEMENT OF THE CENTRAL NORADRENERGIC SYSTEM IN CHOLINERGIC STIMULATION OF THE PITUITARY-ADRENAL RESPONSE

Involvement of the central adrenergic system in stimulation of the hyp othalamic-pituitary-adrenal (HPA) axis by carbachol, a cholinergic mus carinic agonist, was assessed indirectly through corticosterone secret ion. Carbachol (2 mu g) given intracerebroventricularly or intraperito neally evoked a dose-related increase in serum corticosterone levels. On a molar basis, carbachol given icy was considerably more active tha n when injected ip, indicating its central site of action. The cortico sterone response to icy carbachol was significantly reduced by pretrea tment of rats 15 min earlier with prazosin, an alpha(1)-adrenergic rec eptor antagonist. Pretreatment with yohimbine, an alpha(2)-adrenergic antagonists, did not significantly affect the carbachol-induced cortic osterone response. Propranolol, a beta-adrenergic blocker, given icy o r ip significantly impaired the carbachol-elicited corticosterone secr etion. The selective noradrenergic neurotoxin DSP-4 (50 mg/kg) given i p 8 days before the experiment, also potently diminished the carbachol -induced rise in serum corticosterone levels. Carbachol markedly incre ased, while DSP-4 significantly diminished the hypothalamic noradrenal ine levels. Likewise, DSP-4 significantly impaired the carbachol-induc ed rise in hypothalamic noradrenaline levels. Our present results indi cate that the central adrenergic system is involved in the cholinergic muscarinic stimulation of the pituitary-adrenocortical response. Both hypothalamic noradrenaline and adrenergic alpha(1)- and beta-receptor s are significantly involved in the carbachol-induced HPA response.