Reversal of Nicotine Withdrawal Signs Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Male Mice

通过对雄性小鼠 α4β2 烟碱乙酰胆碱受体进行正向变构调节来逆转尼古丁戒断症状

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作者:Ayman K Hamouda, Asti Jackson, Deniz Bagdas, M Imad Damaj

Methods

Spontaneous nicotine withdrawal in nicotine-dependent ICR male mice was established 18-24 h after termination (minipump removal) of 14 days infusion of nicotine. After that (day 15), spontaneous signs of nicotine withdrawal were examined in the following order: anxiety-like behaviors, somatic signs, and then hyperalgesia using previously published behavioral protocols. Fifteen minutes before withdrawal signs testing, mice received a subcutaneous acute injection of vehicle or dFBr at the doses of 0.02, 0.1, and 1 mg/kg to determine the effect of dFBr on nicotine withdrawal symptoms.

Results

dFBr produced dose-dependent reversal of nicotine withdrawal signs in mouse model of spontaneous nicotine withdrawal. Implications: Positive allosteric modulators of nAChR such as dFBr reduce nicotine withdrawal symptoms supporting the potential clinical use of this novel class of nAChR-based therapeutics as smoking cessation aid.

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