Figure 1
EFhd2 is a resilience factor for the establishment of alcohol drinking, the escalation of alcohol consumption and the sedating effects of alcohol. EFhd2 knockout (KO; n=11) and wild-type (WT; n=10) mice were tested in a free-choice two-bottle drinking paradigm for their alcohol consumption. (a) Amount of alcohol consumed at different concentrations of the drinking fluid. (b) Preference of alcohol versus water (*P<0.05, **P<0.01; ***P<0.001). (c) Spontaneous escalation of 16 vol. % alcohol consumption after chronic drinking and alcohol deprivation effect (ADE) in EFhd2 KO (n=11) and WT (n=10) mice. After continuous drinking, animals were withdrawn from alcohol for 3 weeks (dotted lines) and reinstated for 4 days. (d) Average alcohol consumption as area under the curve (AUC) 4 days before and after withdrawal indicates an alcohol deprivation effect in WT mice, but not in EFhd2 KO mice ($P<0.05; &P<0.001 vs chronic consumption). (e) Spontaneous escalation in EFhd2 KO mice is confirmed in alcohol preference vs water (*P<0.05, $P<0.01; #P<0.001 vs WT). (f) Sucrose (sweet) preference and quinine (bitter) avoidance test in a free-choice two-bottle drinking paradigm indicates no difference between EFhd2 KO and WT mice in taste preference. EFhd2 KO mice show attenuated sedating effects of alcohol in the loss of righting reflex (LORR) test. (g) Latency to lose the righting reflex and (h) duration of sedation in EFhd2 KO (n=19) and WT (n=23) mice (*P<0.05). (i) Blood alcohol concentration in WT (n=8) and EFhd2 KO mice (n=8) after alcohol injection (3.0 g kg−1, intraperitoneal). Over the 2 h tested, there was no difference in alcohol bioavailability between genotypes (P>0.05).
