Chronic Nicotine Treatment Leads to Sustained Stimulation of Tyrosine Hydroxylase Gene Transcription Rate in Rat Adrenal Medulla

Abstract

Nicotine is a powerful stimulant of the sympathoadrenal system, causing the release of peripheral catecholamines and activation of catecholamine biosynthesis. In previous reports, we have studied the mechanisms by which short-term nicotine treatment regulates tyrosine hydroxylase (TH) in adrenal medulla. In this report, we study the effects of chronic nicotine treatment on adrenal TH gene expression. Rats were injected with either saline or nicotine twice per day for up to 14 days. Chronic nicotine treatment elicited long-lasting, dose-dependent increases in the levels of adrenal TH mRNA, TH protein, and TH activity. In contrast, a single injection of nicotine elicited only a small increase in adrenal TH mRNA levels, which was transient and did not result in the induction of TH enzyme.Chronic nicotine administration also elicited a sustained increase in adrenal TH gene transcription rate, which persisted for up to 7 days after the final nicotine injection. This sustained transcriptional response correlated with a modest sustained increase in adrenal TH AP1 binding, but not in the levels of Fra-2 or other fos or jun proteins. These results demonstrate that repeated nicotine injections administered chronically over 1 to 2 weeks lead to sustained stimulation of the TH gene and consequent induction of TH gene expression in rat adrenal medulla. These studies support the hypothesis that chronic nicotine administration produces long-lasting cellular changes in adrenal medulla that lead to sustained transcriptional responses.

Nicotine exposure affects mother's and pup's nutritional, biochemical, and hormonal profiles during lactation in rats

“…This phenomenon would explain lower TH expression as well as higher levels of catecholamines in association with lower levels of cholinergically stimulated release. In contrast, other studies have shown higher TH expression and activity in the adrenal medulla of rats exposed acutely (Tank et al 1998, Sterling & Tank 2001 or chronically to nicotine (Sun et al 2003). Cheng et al (2005) observed no changes in Th mRNA levels in rats that were chronically exposed.…”

Differential effects of TRPV1 receptor ligands against nicotine-induced depression-like behaviors

“…It has also been predicted that a characteristically rapid desensitization of the direct target nAChRs, following their initial activation by NC, may yield contradicting depression-related behavioral alterations [45]. Furthermore, the NC-induced depression-related behavioral alterations may occur in accordance with neuroendocrine alterations such as the levels of brain monoamines and stress hormones, in which the time course coincides at least partly with the neuroendocrine responses caused by the depression-inducing stressors, regardless of the behavioral outcome [46,47]. …”

Nicotine (NC)-induced "depressive" behavioral symptoms and effects of antidepressants including cannabinoids (CBs)

“…Although the mechanisms underlying the appearance of these dual contrary behavioral -sympathoadrenal system, increased stress hormones, etc.) have been reported to accompany NC treatment, and seem to be affected by differing conditions such as the number of NC administrations (Kirch et al, 1987;Morse, 1989;Sun et al, 2003). Furthermore, the time course of those of these dual behavioral effects.…”