Effect of the α4β2∗ nicotinic acetylcholine receptor partial agonist varenicline on dopamine release in β2 knock-out mice with selective re-expression of the β2 subunit in the ventral tegmental area

We studied the effects of 1 mg/kg doses of nicotine and the α4β2* nicotinic acetylcholine receptor (nAChR) partial agonist, varenicline, on extracellular dopamine (DA) levels in the nucleus accumbens (NuAcc) of lentivirally vectorized male mice. Three separate experimental groups were injected with a lentiviral vector transducing the ventral tegmental area (VTA): wild-type C57BL/6J mice with a vector expressing eGFP only, β2 knock-out mice (β2KO) with the eGFP-only vector, and β2KO mice with a bicistronic vector reintroducing β2 and eGFP into the VTA as recently described (Maskos et al., 2005). Our results suggest that the neurochemical effects of varenicline as measured by using microdialysis in awake, freely moving mice are mainly mediated via β2* nAChR subunits localized in the VTA.