Interstimulus interval determines whether ethanol produces conditioned place preference or aversion in mice

DBA/2J mice were exposed to distinctive floor stimulus (CS+) and ethanol (2 g/kg) in a place conditioning paradigm. A different floor stimulus (CS-) was presented with saline. Mice injected just before or 30 min before CS exposure (Groups 0, -30) showed conditioned place preference, whereas mice injected right after exposure to the CS (Group 5) displayed place aversion (Experiment 1). None of the other groups (-120, -60, 15, 60) showed place conditioning. Handling and saline injection given just before or after CS exposure were unable to produce place conditioning (Experiment 2). However, there was a positive relationship between ethanol concentration (10% vs. 20%) and test performance, suggesting that peritoneal irritation influences place conditioning (Experiment 3). Overall, these findings support the suggestion that intraperitoneal injection of ethanol produces an initial short-duration aversive effect that is followed by a longer lasting positive motivational effect.