ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026
Sex-dependent role of the ventral hippocampus, but not its projection to the medial prefrontal cortex, in a novel operant conflict-driven ethanol choice task.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Sex differences in approach-avoidance decision making with sucrose rewards are well documented, with males exhibiting greater conflict approach behavior and females exhibiting greater conflict avoidance. Consistent with this, previous work has shown that approach bias under conflict in males reliably predicts persistent operant ethanol self-administration under punishment. In females, however, heightened vulnerability to ethanol reward-seeking in the face of aversive consequences is observed, despite their tendency to avoid sucrose reward paired with punishment. We sought to further investigate this seeming paradox by designing an ethanol-based choice decision-making task wherein rats could lever press for a large ethanol reward accompanied by shock (of increasing intensity) or for a small ethanol reward on discrete trials. We further probed the role of the ventral hippocampus (vHPC), a known hub in approach-avoidance conflict resolution and its projections to the medial prefrontal cortex (mPFC) in the ethanol choice task, using a chemogenetics approach. We found that vHPC CA1 inactivation caused a relative shift towards choosing the large ethanol plus shock lever in males, and a relative shift towards choosing the safe small ethanol option in females at high levels of conflict. The pathway manipulation, however, had no influence on choice behavior. These findings implicate the vHPC CA1 in modulating ethanol choice during high conflict situations, with opposing effects in males and females.
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