Adrenocorticotropin response and nicotine-induced norepinephrine secretion in the rat paraventricular nucleus are mediated through brainstem receptors.
Nicotine is a potent stimulus for the secretion of ACTH, and norepinephrinergic neurons originating in the brainstem are involved. Prior reports using in vivo microdialysis in alert rats have shown that nicotine, administered i.p. or into the fourth ventricle, stimulated the release of norepinephrine (NE) into the hypothalamic paraventricular nucleus (PVN), the site of neurons containing CRH. In the present studies, rats received an i.v. infusion of nicotine into the jugular vein on alternate days during their active (dark) phase; therefore, direct correlations between the levels of NE microdialyzed from the PVN and plasma ACTH could be made in each animal. Nicotine administered i.v. (0.045-0.135 mg/kg) elicited dose-dependent increases in both NE and ACTH (P < 0.01). A significant correlation was found between nicotine-stimulated NE release in the PVN and ACTH secretion (r = 0.91, P < 0.01). To address whether the site(s) of action of nicotine was on presynaptic receptors on NE terminals in the PVN or on receptors on neurons in brainstem regions accessible from the fourth ventricle, the nicotinic cholinergic antagonist, mecamylamine (0.1-4.8 microg), was microinjected directly into the PVN or into the fourth ventricle before nicotine infusion. Fourth-ventricular administration of mecamylamine (1.6 microg) or higher, before i.v. nicotine (0.09 mg/kg), completely blocked both NE release in the PVN (IC50 = 0.64 microg) and ACTH secretion (IC50 = 0.40 microg) (P < 0.01, compared with vehicle before nicotine), whereas it was ineffective when injected directly into the PVN. The results demonstrate that the nicotinic cholinergic receptors in the brainstem, rather than presynaptic receptors within the PVN itself, mediate nicotine-stimulated PVN NE release and ACTH secretion.
Fu
Y
Y
Endocrine-Neuroscience Laboratories, Minneapolis Medical Research Foundation, Minnesota 55404, USA.
Matta
S G
SG
Valentine
J D
JD
Sharp
B M
BM
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D017551:Microdialysis; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D000324:Adrenocorticotropic Hormone; D009638:Norepinephrine