Nicotine Induced Circadian Entrainment as a Novel Target for Smoking Cessation
Reimink, Katie M.
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Circadian rhythms are daily fluctuating levels of behavioral and biological activity. Specific time cues, called zeitgebers, mediate these rhythms , most common of which, is the sun. Circadian rhythms have been shown to be modulated by the daily administration of dependence producing drugs, indicating that drugs of abuse can act as a zeitgeber. Previous studies have shown that nicotine (Gillman, et al., 2008), cocaine (White, et al., 2000), fentanyl (Gillman, et al., submitted manuscript), methamphetamine (Kosobud, et al., 1998), and ethanol (Gillman et al., unpublished data) have been able to modulate an organism’s daily activity around the administration of the drug, a behavior that persists even in the absence of the drug. If an organism’s behavior is constructed around the presence of a drug zeitgeber, than the circadian entrainment to the drug cue may be perpetuating the abuse of the drug. Drug-induced entrainment , specifically nicotine, shows both anticipatory activity (PRE) beginning 2 hours before the injection time and a drug-evoked increase in post-injection (POST) activity. It has been proposed that 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), blocks the effects of nicotine at the synaptic level and has been therapeutically used to help decrease nicotine consumption in the rat model. It was used in this experiment as a treatment drug to determine the role of the nAChRs in circadian entrainment.