Evidence for the important role of CHRNB2 in smoking cessation is consistent with the animal studies demonstrating the involvement of β2 subunit-containing nAChRs in nicotine-mediated release of dopamine and in the nicotine withdrawal syndrome. Nicotine reduces, and withdrawal increases the brain stimulation reward-thresholds in rodents (27,28), effects which are mediated largely via α4β2 nAChRs (29). Further, compared with WT mice, knockout mice lacking the β2 subunit exhibit attenuated nicotine self-administration and reduced nicotine stimulated dopamine release in the ventral striatum (30), as well as reductions in conditioned nicotine reinforcement (31,32). Effects of nicotine, and nicotine withdrawal, on cognitive function are also attenuated in β2 knockout mice (33,34).
