Altered responsiveness to psychostimulants upon ablation of Vmat2 gene expression in NeuroD6 VTA neurons. Color coding: Vmat2lox/lox;NEX-Cre-wt (Ctrl) in white; Vmat2lox/lox;NEX-Cre-tg(cKO) in green. A, Weight curve for Ctrl (N = 14) and cKO (N = 23) mice. Data presented as mean weight in grams for each week ± SEM (+p < 0.05 effect of genotype; ###p < 0.001, effect of age). B, Baseline locomotion in novel environment. Ctrl (N = 17) and cKO (N = 17). Data expressed as mean distance moved in 5-min bins ± SEM (###p < 0.001, effect of time). C, Sucrose preference expressed as percentage of preference for sucrose over tap water ± SEM. Ctrl (N = 14) and cKO (N = 21; ###p < 0.001 effect of sucrose concentration). D, Ethanol preference expressed as percentage of preference for ethanol solution over tap water ± SEM. Ctrl (N = 14) and cKO (N = 14; ###p < 0.001 effect of ethanol concentration, §§§p < 0.001 3% vs 6% and 10% in ctrl mice). E, Cocaine-induced locomotion. Top, Administration schedule. Bottom, Average distance moved 1 h after injection of saline and 5, 10, 20 mg/kg of cocaine; Ctrl (N = 14) and cKO (N = 21) mice. Data expressed as total distance moved during the 1-h recording period ± SEM (###p < 0.001 effect of session). F, Amphetamine-induced locomotion. Top, Administration schedule. Bottom, Average distance moved 1.5 h after injection; Ctrl (N = 17) and cKO mice (N = 17). Data presented as mean of total distance moved in cm ± SEM for each session; ++p < 0.01 effect of genotype, ###p < 0.001 effect of session, *p < 0.05 and ***p < 0.001 cKO versus Ctrl. G, CPP. Illustration of setup and administration schedule. H, J, Preference score displayed as Δsec, the difference between time spent in drug-paired compared during pretest and test ± SEM, positive value indicates preference (cocaine: Ctrl N = 12, cKO N = 15; amphetamine: Ctrl N = 13, cKO N = 16). I, K, Cocaine-induced and amphetamine-induced locomotion during conditioning in the CPP setup displayed as distance moved in 30 min ± SEM (cocaine: Ctrl N = 12, cKO N = 15; amphetamine: Ctrl N = 15, cKO N = 17, +p = 0.031 effect of genotype, ##p = 0.006, ###p < 0.001 effect of session). Ctrl, Control; cKO, conditional knockout; CPP, Conditioned place preference.