Further studies on the stimulatory action of nicotine on adrenocortical function in the rat.

The aim of the present study was to further characterize the site of action of nicotine-induced hypothalamo-hypophyseal-adrenal (HHA) activation. A systemic injection of nicotine in concentrations of 65-2,100 micrograms/kg elevated serum corticosterone (CS) concentrations in a time and dose-dependent manner. Serum ACTH levels were also significantly increased. Pretreatment with dexamethasone (40 micrograms/kg) or the nicotinic antagonist, mecamylamine (1 mg/kg), abolished the ACTH and CS secretory responses to nicotine. Intracerebroventricular administration of antinicotinic acetylcholine receptor antibodies, prepared from the serum of myasthenia gravis patients, completely inhibited the nicotine-induced HHA activation. Bilateral lesions of the paraventricular nucleus similarly inhibited the nicotine-induced adrenocortical activity. These results suggest that nicotine activates the HHA axis by a central mechanism which ultimately requires the integrity of the paraventricular nucleus. Moreover, these findings indicate that the nicotinic adrenocortical effect is mediated specifically through activation of central nicotinic cholinergic receptors.