Figure 3
Low anxiety and high alcohol consumption in EFhd2 knockout (KO) mice can be reversed by chronic subcutaneous (s.c.) treatment with the anxiogenic drug β-carboline-3-carboxylate ethyl ester (β-CCE). β-CCE was administered s.c. by osmotic minipumps at a rate of 1.5 mg kg−1 per day. After 8–9 days of administration, the elevated plus maze (EPM) test revealed a reversal of the low-anxiety phenotype of EFhd2 KO mice (n=7 per group) to the level of wild-type (WT, n=8 and 9 per group) animals. (a) Time spent in the open (OA) and closed arm (CA) or centre (Ctr) of the EPM (*P<0.05). (b) Alcohol consumption in a two-bottle free-choice drinking paradigm in mice with chronic treatment with β-CCE or vehicle (***P<0.001; #P<0.05). (c) Dopamine basal levels in the nucleus accumbens (Nac) and prefrontal cortex (PFC) prior to alcohol treatment. EFhd2 is required for basal dopaminergic tone in the Nac, but not in the PFC of mice (*P<0.05). (d) EFhd2 limits the alcohol-induced increase in extracellular dopamine levels in the Nac, but not in the PFC of mice. Extracellular dopamine levels after acute alcohol (2 g kg−1, intraperitoneal) treatment in EFhd2 KO (n=9) and WT (n=9) mice in (d) the Nac and (e) PFC (*P<0.05, §P<0.01 vs WT).
