Selective administration of nicotine into catecholaminergic regions of rat brainstem stimulates adrenocorticotropin secretion.
Nicotine (Nic) is a potent stimulus for ACTH secretion, and this response appears to be mediated by central catecholamine secretion. We have previously shown that fourth ventricular administration of Nic rapidly elevated plasma ACTH levels, that a nicotinic cholinergic antagonist, mecamylamine, instilled into the fourth ventricle inhibited the ACTH response to iv Nic, and that Nic stimulated norepinephrine secretion in the hypothalamic paraventricular nucleus. Thus, the present investigations sought to identify Nic-responsive regions in the brainstem that give rise to ascending catecholaminergic afferents resulting in ACTH secretion. Chronic brain and jugular cannulae were implanted, and Nic (50 nl over 30 sec) was infused into the locus coeruleus (LC), nucleus of the solitary tract (NTS -C2 or -A2 regions), C1, or A1 cell regions of freely moving, adult male rats. Injection of Nic (free base, 0.25-10 micrograms) into either the C2 or A2 region of NTS resulted in a dose-dependent increase in plasma ACTH. In contrast, C1 was unresponsive and A1 only showed responses to the highest doses of Nic (5 or 10 micrograms). In LC, Nic in doses of 2.5 micrograms or higher was required to elevate plasma ACTH. This dose is approximately 10-fold greater than that required in NTS-A2. Finally, mecamylamine (0.25 mg/kg body wt, iv), administered 2 min before Nic, abolished the ACTH responses in both C2 and A2 and significantly reduced the 7-min peak ACTH response in LC (P < 0.05). In summary, microinjection of Nic selectively activated the brainstem regions under investigation, with a rank order of sensitivity to Nic that was NTS-A2 > NTS-C2 > LC > A1 > C1 = cerebrospinal fluid. Therefore, systemically administered Nic appears to activate multiple catecholaminergic brainstem regions that are involved in mediating ACTH secretion.
Matta
S G
SG
Endocrine Neurosciences Laboratories, Minneapolis Medical Research Foundation, Minnesota 55404.
Foster
C A
CA
Sharp
B M
BM
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D002395:Catecholamines / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008845:Microinjections; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D008464:Mecamylamine; D009538:Nicotine; D000324:Adrenocorticotropic Hormone