NICOTINE-INDUCED CFOS EXPRESSION IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS IS DEPENDENT ON BRAIN-STEM EFFECTS - CORRELATIONS WITH CFOS INCATECHOLAMINERGIC AND NONCATECHOLAMINERGIC NEURONS IN THE NUCLEUS-TRACTUS-SOLITARIUS

Systemically administered nicotine elicits ACTH release indirectly by acting on neurons in brainstem catecholaminergic regions known to send afferent projections to the paraventricular nucleus of the hypothalam us (PVN), the site of CRH neurons involved in initiating ACTH secretio n. The present study in rats examined 1) the relationship between dose -dependent expression of cFos in the PVN and that in the nucleus of th e solitary tract (NTS)-A(2), NTS-C-2 and locus coeruleus (LC), after i v nicotine (0.045-0.18 mg/kg, administered at 0.09 mg/kg per min); 2) the dependence of PVN cFos expression on the effects of nicotine in br ainstem, using the nicotinic cholinergic antagonist, mecamylamine, adm inistered into the fourth ventricle; and 3) the extent of catecholamin ergic involvement in the effect of nicotine on the PVN, measured by im munocytochemical double-labeling for cFos and tyrosine hydroxylase (TH ), the rate-limiting enzyme in catecholamine synthesis. The results sh owed that the magnitude of cFos expression was dependent on the dose o f nicotine in all regions studied (P < 0.0006); however, at the two lo west doses, only the NTS and CRH-containing region of the PVN expresse d cFos, whereas the LC and the rest of the PVN were activated only by higher doses. Nicotine also elicited a dose-dependent increase in cFos expression in the TH+ neurons of the NTS, with C-2 more sensitive tha n A(2). Interestingly, the majority of NTS neurons expressing cFos wer e noncatecholaminergic, implicating other transmitter systems. Fourth ventricular mecamylamine completely blocked nicotine-induced cFos expr ession throughout the NTS, as well as the PVN. The results provide fur ther support for the idea that catecholaminergic afferents from the NT S, but not the LC, play a significant, albeit not an exclusive, role i n the activation of the PVN in response to nicotine.