Effect of the alpha4beta2* nicotinic acetylcholine receptor partial agonist varenicline on dopamine release in beta2 knock-out mice with selective re-expression of the beta2 subunit in the ventral tegmental area.

We studied the effects of 1 mg/kg doses of nicotine and the alpha4beta2* 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, beta2 knock-out mice (beta2KO) with the eGFP-only vector, and beta2KO mice with a bicistronic vector reintroducing beta2 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 beta2* nAChR subunits localized in the VTA.