Ethanol-induced conditioned partner preference in female mice

Drinking behavior and social context are intimately intertwined. Peer relations can promote drinking. Conversely, alcohol promotes social interaction. The present study tested female mice for ethanol-induced conditioned partner preference. Ovariectomized (OVX) C57Bl/6 females with chronic estradiol replacement (OVX+E) received saline or ethanol (1, 2 or 4 g/kg) ip and were paired 4× for 30 min each with 1 of 2 stimulus females. The test female was paired with the CS− stimulus female following saline, and was paired with the CS+ female following ethanol. After pairing, we measured proximity of the test female to the CS+ and CS− females in a 10’ test. In a second study, OVX and OVX+E females were tested for conditioned partner preference (CS+ vs. CS−) in response to 2.5 g/kg ethanol. In separate groups of mice, both test and stimulus females (IS+) received ethanol during pairing to determine if test mice develop conditioned partner preference for another intoxicated mouse. OVX+E test females showed conditioned partner preference for the CS+ female in response to ethanol at 2 g/kg (change in preference score for CS+: +86.6 ± 30.0 s/10 min), but not at 0, 1 or 4 g/kg. At 2.5 g/kg ethanol, OVX+E females developed conditioned partner preference for either IS+ (+63.6 ± 24.0 s) or CS+ females (+93.8 ± 27.1 s). OVX test females demonstrated ethanol-induced conditioned partner preference only for the IS+ female (+153.8 ± 32.0 s). These data demonstrate that ethanol promotes social preference in female mice, and that estradiol enhances this effect.

► We tested effects of ethanol on conditioned partner preference in female mice to explore social dimensions of substance abuse. ► Test females showed a conditioned preference for a stimulus female (CS+) paired with ethanol. ► Conditioned partner preference was maintained if the CS+ female was also intoxicated. ► Estrogen replacement in ovariectomized females facilitated ethanol-induced conditioned partner preference.