Nicotine Induced Circadian Entrainment as a Novel Target for Smoking Cessation
Reimink, Katie M.
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Circadian rhythms have been shown to be modulated by the daily administration of dependence forming drugs. Daily nicotine administration in rats has been shown to act as a zeitgeber for the entrainment of circadian activity rhythms. Nicotine-induced entrainment shows both anticipatory activity (PRE) beginning 2 hr before the injection time and a drug-evoked increase in post-injection (POST) activity. A treatment for nicotine abuse may lie in the ability to eradicate entrainment to the drug administration time. Mecamylamine (MEC), a nicotinic acetylcholine receptor antagonist (nAChR), has been therapeutically used to help decrease nicotine consumption. The present study used 48 adult female Sprague-Dawley rats (Rattus norvegicus) separated equally into 6 groups: half dosed with nicotine and the other with saline with 3 different treatment possibilities, "cold turkey'', saline injections, and MEC. The subjects were housed in wheel boxes under constant dim light and rate limited feeding. The rats underwent two subcutaneous injection series (1 mllkg nicotine or 1 mllkg saline, corresponding to grOHP membership), followed by 2 treatment days, and 4 baseline days administered over 36 days. Most interestingly, MEC treatment showed significant decreases in nicotine POST entrainment activity during the treatment days, with increased PRE withdrawal-like activity, whereas the cold turkey and saline treatments showed no changes in PRE or POST activity in response to treatment. The partial, but not complete, elimination of entrained behavior provides evidence that separate oscillators modulate drug seeking and drug-evoked behaviors.