Involvement of the central noradrenergic system in cholinergic stimulation of the pituitary-adrenal response

Involvement of the central adrenergic system in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by carbachol, a cholinergic muscarinic agonist, was assessed indirectly through corticosterone secretion. Carbachol (2 micrograms) given intracerebroventricularly or intraperitoneally evoked a dose-related increase in serum corticosterone levels. On a molar basis, carbachol given i.c.v. was considerably more active than when injected i.p., indicating its central site of action. The corticosterone response to i.c.v. carbachol was significantly reduced by pretreatment of rats 15 min earlier with prazosin, an alpha 1-adrenergic receptor antagonist. Pretreatment with yohimbine, an alpha 2-adrenergic antagonists, did not significantly affect the carbachol-induced corticosterone response. Propranolol, a beta-adrenergic blocker, given i.c.v. or i.p. significantly impaired the carbachol-elicited corticosterone secretion. 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 increased, while DSP-4 significantly diminished the hypothalamic noradrenaline levels. Likewise, DSP-4 significantly impaired the carbachol-induced rise in hypothalamic noradrenaline levels. Our present results indicate 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-receptors are significantly involved in the carbachol-induced HPA response.