Relationship between voluntary ethanol drinking and approach-avoidance biases in the face of motivational conflict: novel sex-dependent associations in rats.

Rationale: Aberrant approach-avoidance conflict processing may contribute to compulsive seeking that characterizes addiction. Exploration of the relationship between drugs of abuse and approach-avoidance behavior remains limited, especially with ethanol.

Objectives: To investigate the effects of voluntary ethanol consumption on approach-avoidance conflict behavior and to examine the potential approach/avoidance bias to predict drinking in male and female rats.

Methods: Long-Evans rats consumed ethanol for 5 weeks under the intermittent access two-bottle choice (IA2BC) paradigm. Approach-avoidance tendencies were assessed before and after IA2BC drinking using a previously established cued approach-avoidance conflict maze task and the elevated plus maze (EPM).

Results: Female rats displayed higher consumption of and preference for ethanol than males. In the conflict task, males showed greater approach bias towards cues predicting conflict than females. In females only, a median split and regression analysis of cued-conflict preference scores revealed that the more conflict-avoidant group displayed higher intake and preference for ethanol in the first few weeks of drinking. In both sexes, ethanol drinking did not affect cued-conflict preference, but ethanol exposure led to increased time spent in the central hub in the males only. Finally, anxiety levels in EPM predicted subsequent onset of ethanol drinking in males only.

Conclusions: Our results highlight sex and individual differences in both drinking and approach-avoidance bias in the face of cued conflict and further suggest that cued-conflict preference should be examined as a potential predictor of ethanol drinking. Ethanol exposure may also affect the timing of decision-making in the face of conflict.