The affective and cognitive signs of nicotine withdrawal are believed to be an important factor in failed cessation attempts and continued use (Koob et al. 1993; Markou et al. 1998). Jackson et al. (2008) measured affective signs of withdrawal and found a loss of anxiety-related behavior and loss of aversion in v2 KO mice. Cognitive withdrawal symptoms, as assessed by the contextual fear conditioning paradigm, were examined in β2 KO mice by Portugal et al. (2008). v2 KO mice withdrawn from nicotine showed no withdrawal-related deficits on contextual fear conditioning (Portugal and Gould 2008) compared to deficits exhibited in wild-type mice. Further, nicotine acting on intact hippocampal β2-containing nAChRs may alter hippocampal function accounting for the withdrawal deficits in contextual fear conditioning (Davis and Gould 2007). Subsequently, Raybuck and Gould found that nicotine withdrawal in β2 KO mice did not produce the trace fear conditioning deficits observed in wild-type mice. Evidence from these studies suggests an important role for β2 containing nAChRs in withdrawal-related deficits in learning and memory (Raybuck and Gould 2009).
