Knockout mice that lack the β2 subunit do not self-administer nicotine and do not show nicotine-stimulated dopamine release in the ventral striatum, implicating its role in mediating nicotine dependence (Besson et al. 2006; Picciotto et al. 1998), however, the β2 KO mice exhibit normal withdrawal symptoms (increased levels of rearing and jumping) (Besson et al. 2006). Marubio et al. (1999) showed that β2 KO mice display a reduction in high-affinity binding sites, a reduced antinociceptive effect to nicotine on the hot-plate test, and diminished sensitivity to nicotine in the tail-flick test, supporting a role for this subunit in the antinociceptive effects of nicotine.
