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Publication : The β3 subunit of the nicotinic acetylcholine receptor is required for nicotine withdrawal-induced affective but not physical signs or nicotine reward in mice.

First Author  Jackson AB Year  2019
Journal  Pharmacol Biochem Behav Volume  183
Pages  1-5 PubMed ID  31145916
Mgi Jnum  J:289269 Mgi Id  MGI:6434928
Doi  10.1016/j.pbb.2019.05.003 Citation  Jackson AB, et al. (2019) The beta3 subunit of the nicotinic acetylcholine receptor is required for nicotine withdrawal-induced affective but not physical signs or nicotine reward in mice. Pharmacol Biochem Behav 183:1-5
abstractText  Nicotinic acetylcholine receptors (nAChRs) are the primary target for nicotine, the addictive component in tobacco products. These pentameric receptors are made up of various subunits which contribute to the diverse functions of nAChR subtypes. The beta3 subunit of the nAChR has been understudied in nicotine dependence, even though it is expressed in brain regions important for drug reward. Therefore, we assessed nicotine dependence behaviors in beta3 wildtype (WT) and knockout (KO) male and female mice. We evaluated nicotine reward in the conditioned place preference (CPP) test and then measured nicotine withdrawal signs after chronic exposure to the drug. For the withdrawal studies, mice were continuously infused with 24mg/kg/day of nicotine using surgically implanted osmotic mini-pumps for 14days. Mini-pumps were removed at day 15, and withdrawal signs (somatic signs, hyperalgesia, anhedonia-like measure using the sucrose preference test and anxiety-like behaviors using the light dark boxes) were collected at 24h intervals for three days following spontaneous withdrawal of nicotine. Nicotine-induced CPP did not differ between beta3 KO and WT mice. beta3 KO mice displayed similar somatic symptoms and hyperalgesia compared to WT mice but showed significant absence in affective (anhedonia and anxiety-like behaviors) withdrawal signs in nicotine-dependent mice. These observations suggest that the beta3 nicotinic subunits do not seem to influence nicotine reward but plays an important role in affective nicotine withdrawal signs. Given the health burden of tobacco use disorder and the modest effect of smoking cessation aids, it is important to understand underlying factor contributing to nicotine dependence. The results of this study will further our knowledge of the role of the beta3 nAChR subunit in nicotine reward and withdrawal behaviors in hopes of finding new molecular targets for smoking cessation aids.
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