Sensitization of ethanol‐induced place preference as a result of up‐regulation of type 1 inositol 1,4,5‐trisphosphate receptors in mouse nucleus accumbens

This study involved mice that received 4 days of ethanol (EtOH) vapor inhalation and then were assessed for type 1 inositol 1,4,5‐trisphosphate receptor (IP₃Rs‐1) expression and the development of EtOH‐induced place preference at various time points in withdrawal. IP₃R‐1 protein was found to be significantly increased in the nucleus accumbens (NAcc) of mice immediately after 4‐day EtOH vapor inhalation, while it significantly reduced to the control level during the next 3 days of withdrawal from EtOH inhalation. EtOH (2 g/kg, i.p.)‐induced place preference after 3 days of withdrawal from EtOH vapor inhalation increased dose dependently for 4 days, which was significantly inhibited by 2‐aminophenoxyethane‐borate, an antagonist for IP₃Rs. EtOH conditioning significantly increased, compared to alcohol‐naïve control mice, both IP₃R‐1 protein and the release of dopamine in the NAcc of mice after 3 days of withdrawal from EtOH vapor inhaled for 4 days, and this increase of IP₃R‐1 protein was completely abolished by intracerebroventricular injection of FK506, an inhibitor for calcineurin. These results indicate that the sensitization of EtOH‐induced place preference is due to up‐regulated IP₃R‐1 via calcineurin‐mediated pathway after enhanced release of dopamine in the NAcc on EtOH administration during EtOH conditioning.