Genes encoding nAChRs mediate variability in many of the behavioral effects of nicotine. KO mice for nAChR subunits α3–α9 and β2–β4 have shown that the deletion of these genes alters many effects of nicotine. Unlike wild-type animals, mice lacking the α4 and β2 subunits do not self-administer nicotine and do not show nicotine-induced increases of dopamine in the ventral stratum.72,73 In addition, β2 KO mice self-administer cocaine but fail to maintain self-administration when cocaine is switched to nicotine,72 whereas α4 KO mice exhibit a prolonged motor response to cocaine.73 Together, the findings from α4 and β2 KO mice provide evidence that α4β2* (* indicates another undetermined subunit) nAChRs are required for proper regulation of dopamine release and maintenance of self-administration and reinforcement.
