Nicotine activates NPY and catecholaminergic neurons in brainstem regions involved in ACTH secretion.
Nicotine rapidly and potently stimulates ACTH secretion via a centrally mediated mechanism. The purpose of the current study was to identify the phenotype of nicotine-sensitive neurons in brainstem catecholaminergic regions previously shown to be responsive to nicotine. Immunocytochemical double-labeling was used to detect c-Fos expression in neurons positive for activin, galanin, or neuropeptide Y (NPY), in comparison to those containing tyrosine hydroxylase (TH, catecholaminergic biosynthetic enzyme). These neuropeptides were chosen because (1) each is located in nicotine-sensitive brainstem regions, (2) neurons containing each of these peptides project to the hypothalamic paraventricular nucleus, and (3) each has been shown to affect ACTH secretion. Freely moving, adult, male rats received an intravenous (i.v.) infusion of saline or nicotine (0.045 mg/kg over 30 s or 0.135 mg/kg over 90 s) and were cardiac perfused 60 min thereafter. Nicotine significantly increased c-Fos expression in a dose-dependent manner in the brainstem regions examined. In nucleus tractus solitarius (NTS)-A2 and NTS-C2, both NPY+ and TH+ neurons responded to the lower dose of nicotine, whereas the activin and galanin neurons in these regions were unresponsive to either dose of nicotine. In contrast, the higher dose of nicotine was required to activate NPY+ neurons in the A1 region and both NPY+ and galanin+ neurons in the locus coeruleus; the C1 region was unresponsive to nicotine. Since plasma ACTH is elevated by the low dose of nicotine and only NTS neurons are activated by this dose, NPY projections from the NTS are likely to contribute to nicotine-stimulated ACTH secretion, in addition to the previously described catecholaminergic neurons.
Matta
S G
SG
Minneapolis Medical Research Foundation, Department of Medicine, Hennepin County Medical Center and University of Minnesota, 55404, USA. matta001@maroon.tc.umn.edu
Valentine
J D
JD
Sharp
B M
BM
D000324:Adrenocorticotropic Hormone / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects*; D002395:Catecholamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009478:Neuropeptide Y / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats
D002395:Catecholamines; D009478:Neuropeptide Y; D009538:Nicotine; D000324:Adrenocorticotropic Hormone