These in vitro studies are being extended in transgenic mouse model studies to clarify the behavioral mechanisms underlying these associations. For example, α5 knock-out mice respond for higher doses of intravenously self-administered nicotine infusions compared to wild-type mice, suggesting that the α5 subunit may be important in the experience of toxicity associated with high nicotine doses (Fowler et al. 2011). In another study, α5 KO mice were implanted with osmotic mini-pumps containing nicotine for 14 days, followed by precipitated withdrawal with mecamylamine (Jackson et al. 2008). The α5 KO mice showed a reduction in somatic signs only, suggesting that this subtype is involved with the physical measures of withdrawal symptoms but not affective withdrawal signs (Jackson et al. 2008). Salas and colleagues examined α5 KO mice chronically treated with nicotine by osmotic mini-pumps or in their drinking water, followed by mecamylamine precipitated withdrawal. Consistent with the results of Jackson and colleagues, the lack of the α5 subunit abolished the somatic symptoms of withdrawal to levels exhibited by saline-treated mice, suggesting that the α5 subunit mediates some physical symptoms of nicotine
