Sex differences in the effects of adolescent intermittent ethanol exposure on exploratory and anxiety-like behavior in adult rats

Adolescent intermittent ethanol (AIE) exposure in rodents has been shown to alter adult behavior in several domains, including learning and memory, social interaction, affective behavior, and ethanol self-administration. AIE has also been shown to produce non-specific behavioral changes that compromise behavioral efficiency. Many studies of these types rely on measuring behavior in mazes and other en-closures that can be influenced by animals' activity levels and exploratory behavior, and relatively few such studies have assessed sex as a biological variable. To address the effects of AIE and its interaction with sex on these types of behavioral assays, male and female adolescent rats (Sprague Dawley) were exposed to 10 doses of AIE (5 g/kg, intra-gastrically [i.g.]), or control vehicle, over 16 days (postnatal day [PND] 30-46), and then tested for exploratory and anxiety-like behaviors on the novelty-induced hypophagia (NIH) task in an open field, the elevated plus (EPM) maze, and the Figure 8 maze. AIE reduced activity/exploratory behaviors in males on the anxiety-producing NIH and EPM tasks, but reduced activity in both males and females in the Figure 8 maze, a task designed to create a safe environment and reduce anxiety. Independent of AIE, females engaged in more rearing behavior than males during the NIH task but less in the EPM, in which they were also less active than males. AIE also increased EPM open arm time in females but not in males. These findings demonstrate previously un-recognized sex differences in the effects of AIE on activity, exploratory behavior, and anxiety-like behavior; additionally, they underscore the need to design future behavioral studies of AIE using sex as a variable and with rigorous attention to how AIE alters these behaviors. (C) 2021 Elsevier Inc. All rights reserved.