Impairment of mGluR2 function increases alcohol consumption and preference in iP × iNP F2 rats and Wistar rats. (A) Alcohol consumption (grams of ethanol per kilogram body weight per day) and preference (ethanol/total fluid) were compared across the Grm2 C407* genotype groups (numbers of rats in parentheses) in F2 rats by ANOVA (consumption: df = 2, F = 5.582, P = 0.004; preference: df = 2, F = 5.309, P = 0.005). (B) Grm2 *407 frequencies in the Wistar rats and P rats. Wistar rats (n = 64) and P rats at generation 70 (n = 139) were directly genotyped. Frequency in P rats at generation 30 was inferred from the F2 (n = 380) genotypes and the genotypes of five inbred grandparental P rats of the F2s. The drinking phenotypes were selected every generation before and at generation 30 and every three generations thereafter. (C and D) mGluR2/3 antagonism escalates alcohol self-administration in Wistar rats. After 14 d of training, vehicle or LY341495 (3 mg/kg) (n = 16 per group) were injected (i.p.) 30 min before sessions for five consecutive days. (C) Total numbers of lever presses (mean ± SD) in the 30-min session for each group are shown [two-way ANOVA (treatment and day): F4,
56 = 6.58, P = 0.0002]. (D) numbers of lever presses for 20% alcohol during the intervals when reward was available [F4,
56 = 3.42, P = 0.014]. *Significant by Newman–Keuls test.