Abstract

When nicotine is administered s.c. to rats, tyrosine hydroxylase (TH) enzyme activity and TH gene transcription rate are activated, and TH mRNA and TH protein are induced in adrenal medulla. In this report we test whether nicotine elicits these responses via trans-synaptic mechanisms initiated by the actions of the drug in the brain. Our results demonstrate that intraventricular (i.v.t.) administration of nicotine produces a dose-dependent activation of adrenal TH, which is blocked by i.v.t. administration of hexamethonium, but not by i.p. administration of this nicotinic acetylcholine receptor antagonist. We also show that surgical transection of the splanchnic nerve blocks the activation of adrenal TH by i.v.t.-administered nicotine. Repeated i.v.t. administration of nicotine over a 3-h period (injections spaced 30 min apart) leads to a sustained activation of adrenal TH, suggesting that this central response to nicotine does not readily desensitize. Intraventricular administration of nicotine also stimulates the TH gene transcription rate in rat adrenal medulla. When administered repeatedly i.v.t. or s.c. over 3 h, nicotine induces adrenal TH mRNA. This induction is dependent on innervation of the adrenal medulla, even when the drug is injected s.c. Our results demonstrate that the central effects of nicotine are sufficient to activate TH and induce TH gene expression in rat adrenal medulla. Furthermore, our results suggest that this centrally mediated response to nicotine is essential for the induction of adrenal TH mRNA.