Serotonin neurons in the median raphe nucleus bidirectionally regulate somatic signs of nicotine withdrawal in mice

In chronic smokers, nicotine withdrawal symptoms during tobacco cessation can lead to smoking relapse. rodent models, exposure elicited physical dependence, whereas acute antagonism of nicotinic acetylcholine receptors (nAChRs) immediately precipitated symptoms. Although the central serotonergic system plays an important role in withdrawal, exact raphe nuclei regulating these remain unknown. We used transgenic mice expressing archaerhodopsinTP009 or channelrhodopsin-2[C128S] exclusively neurons selectively manipulate each nucleus. Nicotine were by injection mecamylamine, a nonspecific nAChR antagonist, following consumption. Somatic signs as measures Acute mecamylamine administration significantly increased ptosis occurrence nicotine-drinking compared with that control-drinking mice. Optogenetic inhibition median nucleus (MRN), but not those dorsal (DRN), mimicked observed mecamylamine-precipitated even nicotine-naïve injection. activation MRN nearly abolished The MRN, DRN, are necessary for somatic signs, symptom, and may act potential therapeutic strategy preventing manifestations withdrawal.