Glucocorticoid receptor antagonism blocks ethanol-induced place preference learning in mice and attenuates dopamine D2 receptor adaptation in the frontal cortex.

The glucocorticoid receptor (GR) plays an important role in alcohol (EtOH) self-administration behaviour by its interaction with the dopaminergic (DA) system in the brain. Here we asked whether the GR is also involved in the establishment of EtOH-induced conditioned place preference (CPP) by an interaction with the DA systems in terminal projection areas. We found that the establishment of an EtOH (2 g/kg, i.p.)-induced CPP was paralleled by a decrease in frontal cortex DA D2 receptor mRNA expression, but not in local D2 gene promoter methylation rate. No effect in other brain areas, nor on DA transporter or DA receptor regulating factor mRNA was found. The GR antagonist, RU486 (20 mg/kg, i.p.) blocked the establishment of EtOH CPP and prevented DA D2 receptor adaptations. These data may suggest a role of glucocorticoid receptor mediated D2 adaptations in the establishment of the reinforcing effects of EtOH.