Catecholamines Mediate Nicotine-Induced Adrenocorticotropin Secretion via a-Adrenergic Receptors*

Abstract

Previous studies determined that iv nicotine stimulated ACTH secretion by acting on sites accessible from the fourth ventricle (IV), rather than directly on CRF-containing neurons in the hypothalamus. Brainstem catecholaminergic cell groups, which are accessible from the IV, project to the hypothalamus and stimulate the secretion of CRF and ACTH. Therefore, the studies investigated the role of catecholamines in nicotine-stimulate ACTH secretion. Experiments with the catecholaminergic neurotoxin, 6-hydroxydopamine, demonstrate that the ACTH response to nicotine delivered iv (0.03 or 0.05 mg/kg body wt) or instilled into the IV (1 or 2.5 .mu.g) was significantly reduced in lesioned animals (P < 0.01). Selective inhibitors of epinephrine synthesis, SKF 64139 and 2,3-dichloro-.alpha.-methylbenzylamine (DCMB), significantly reduced (P < 0.01) the ACTH response to 0.05 mg/kg body wt nicotine iv, without affecting median eminence CRF content. Because controversy exists about the effect of DCMB as an .alpha.2 adrenoreceptor antagonist in vivo, this was examined by administering norepinepherine into the third ventricle after DCMBip; DCMB significantly reduced the ACTH response to norepinephrine 0.2 .mu.g (P < 0.05) but not to 0.5 .mu.g. To determine whether .alpha.2 receptors are indeed involved in the ACTH response to nicotine, yohimbine, an .alpha.2 antagonist, was injected into the third ventricle before nicotine injection into the IV. Yohimbine significantly reduced the ACTH response. Thus, the secretion of both hypothalamic epinephrine and, to some extent, norepinephrine is involved in the ACTH response to the activation of catecholaminergic neurons in the IV. Further investigation of the adrenergic receptor(s) involved compared the ACTH response to nicotine (1 .mu.g) instilled into the IV after prazocin (.alpha.1 antagonist), or propranolol (.beta. antagonist) was injected into the third ventricle. Prazocin significantly reduced (P < 0.05) the ACTH response, whereas propranolol was ineffective. Thus, both .alpha.1 and .alpha.2 receptors are involved in mediating the ACTH response to nicotine.