Effects of acute withdrawal on ethanol-induced conditioned place preference in DBA/2J mice

Reexposure to ethanol during acute withdrawal might facilitate the transition to alcoholism by enhancing the rewarding effect of ethanol.

The conditioned place preference (CPP) procedure was used to test whether ethanol reward is enhanced during acute withdrawal.

DBA/2J mice were exposed to an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0, or 1.5 g/kg IP) was paired with a distinctive floor cue (CS+), whereas saline was paired with a different floor cue (CS-). The withdrawal (W) group received CS+ trials during acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before each trial. The no-withdrawal (NW) group did not experience acute withdrawal during conditioning trials but was matched for acute withdrawal experience. Floor preference was tested in the absence of ethanol or acute withdrawal.

All groups eventually showed a dose-dependent preference for the ethanol-paired cue, but development of CPP was generally more rapid and stable in the W groups than in the NW groups. Acute withdrawal suppressed the normal activating effect of ethanol during CS+ trials, but there were no group differences in test activity.

Acute withdrawal enhanced ethanol's rewarding effect as indexed by CPP. Since this effect depended on ethanol exposure during acute withdrawal, the enhancement of ethanol reward was likely mediated by the alleviation of acute withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during acute withdrawal may be a key component in the shift from episodic to chronic ethanol consumption that characterizes alcoholism.