Homer2 Is Necessary for EtOH-Induced Neuroplasticity

AAV-Homer2b reverses the genotypic difference in EtOH-induced adaptations in extracellular glutamate and dopamine. Intra-accumbens infusion of AAV-Homer2b reversed the genotypic difference in the capacity of eight injections of 3 g/kg EtOH to elevate extracellular accumbens levels of glutamate (genotype × AAV × injection number × time, F_(11,495) = 4.99; p < 0.0001) and dopamine (AAV × injection number × time, F_(11,616) = 6.91; p < 0.0001). A, Repeated EtOH elevated extracellular levels of glutamate in AAV-GFP WT mice (injection × time, F_(11,99) = 3.45; p = 0.04). B, A similar effect of repeated EtOH was observed in AAV-Homer2b WT mice (injection × time, F_(11,96) = 3.69; p < 0.0001). C, Repeated EtOH produced a modest reduction in extracellular glutamate in AAV-GFP KO mice (injection × time, F_(11,176) = 3.00; p = 0.001). D, The glutamate response to repeated EtOH in AAV-Homer2b KO was similar to that observed in WT mice (injection × time, F_(11,154) = 3.83; p < 0.0001). E, Repeated EtOH increases extracellular levels of dopamine in AAV-GFP WT mice (injection × time, F_(11,165) = 2.04; p = 0.03). F, This effect was enhanced in AAV-Homer2b WT mice (injection × time, F_(11,132) = 3.44; p < 0.0001). G, Repeated EtOH did not affect extracellular dopamine in AAV-GFP KO mice (injection × time, F_(11,154) = 0.45; p = 0.93). H, The dopamine response to repeated EtOH in AAV-Homer2b KO mice was similar to that observed in AAV-Homer2b WT mice (injection × time, F_(11,165) =5.06; p < 0.0001). Data represent the mean ± SEM percentage change from baseline values (for moles per sample, see Table 1) per 20 min fraction, and the number of animals is in parentheses (injection 1/injection 8). ⁺p < 0.05 versus injection 1 (LSD post hoc tests).