Extrahypothalamic corticotropin-releasing hormone mediates (-)-nicotine-induced elevation of plasma corticosterone in rats

(-)-Nicotine activates the hypothalamic-pituitary-adrenal axis via an activation of the brainstem catecholaminergic neurons in rats. The present study was undertaken to clarify the mechanisms involved in the (-)-nicotine-induced activation of brainstem catecholaminergic neurons in anesthetized rats. Physostigmine (a cholinesterase inhibitor) (0.31 and 0.77 mumol/animal, i.p.) dose-dependently elevated plasma corticosterone in the presence of scopolamine (a muscarinic receptor antagonist) (2.3 mumol/animal, i.p.). (-)-Nicotine (250 and 500 nmol/animal, i.c.v.) dose-dependently elevated plasma corticosterone with concomitant noradrenaline release in the hypothalamic paraventricular nucleus. The (-)-nicotine (500 nmol/animal, i.c.v.)-induced elevation of corticosterone was abolished by phentolamine (an alpha-adrenoceptor antagonist) (0.66 mumol/animal, i.c.v.), and attenuated by (+/-)-sotalol (a beta-adrenoceptor antagonist) (0.97 mumol/animal, i.c.v.). The (-)-nicotine-induced increases of plasma corticosterone and hypothalamic noradrenaline release were abolished either by hexamethonium (a nicotinic acetylcholine receptor antagonist) (1.8 mumol/animal, i.c.v.), CP-154,526 (butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine) (a selective CRF-1 receptor antagonist) (1.3 mumol/animal, i.c.v.) or indomethacin (a cyclooxygenase inhibitor) (1.2 mumol/animal, i.c.v.). These results suggest that (-)-nicotine elevates plasma corticosterone by CRF-1 receptor- and prostaglandin-mediated noradrenaline release in the paraventricular nucleus in rats. (C) 2003 Elsevier B.V. All rights reserved.