FOS expression induced by an ethanol-paired conditioned stimulus

To identify brain areas involved in ethanol-induced Pavlovian conditioning, brains of male DBA/2J mice were immunohistochemically analyzed for FOS expression after exposure to a conditioned stimulus (CS) previously paired with ethanol (2 g/kg) in two experiments. Mice were trained with a procedure that normally produces place preference (Before: ethanol before the CS) or one that normally produces place aversion (After: ethanol after the CS). Control groups received unpaired ethanol injections in the home cage (Delay) or saline only (Naïve). On the test day, mice were exposed to the 5-min CS 90 min before sacrifice. Before groups showed a conditioned increase in activity, whereas the After group showed a conditioned decrease in activity. FOS expression after a drug-free CS exposure was significantly higher in Before-group mice than in control mice in the bed nucleus of the stria terminalis (Experiment 1) and anterior ventral tegmental area (Experiments 1-2). Conditioned FOS responses were also seen in areas of the extended amygdala and hippocampus (Experiment 2). However, no conditioned FOS changes were seen in any brain area examined in After-group mice. Overall, these data suggest an important role for the mesolimbic dopamine pathway, extended amygdala and hippocampus in ethanol-induced conditioning.