Treadmill Exercise Buffers Behavioral Alterations Related to Ethanol Binge-Drinking in Adolescent Mice

Abstract

The binge-drinking pattern of EtOH consumption, which is frequently observed in adolescents, is known to induce several neurobehavioral alterations, but protection strategies against these impairments remain scarcely explored. We aimed to study the protective role of treadmill physical exercise on the deficits caused after repeated cycles of binge-like EtOH exposure in the cognition, motivation, exploration, and emotion of C57BL/6J mice from adolescence to adulthood. Animals were divided into four groups: control group, exercised group, EtOH group, and exercised + EtOH group (20% in tap water). The exercise was performed for 20 min, 5 days/week at 20 cm/s. Then, animals were submitted to several behavioral tasks. Compared to binge-drinking mice, the exercised + EtOH group exhibited diminished anxiolytic-related behaviors in the elevated plus-maze, enhanced exploratory activity in the open field, reduced preference for alcohol odor when another rewarding stimulus was present (social stimulus) and lower latency to start self-cleaning behaviors in the sucrose splash test. In contrast, other measurements such as habituation learning and working memory were not improved by exercise. Besides, exercise was not able to reduce alcohol consumption across the weeks. In conclusion, physical activity during adolescence and early adulthood could buffer certain neurobehavioral alterations associated with binge-drinking, despite not reducing the quantity of consumed alcohol.

Keywords: adolescence; aerobic exercise; alcohol; behavior; drinking in the dark; mice.

Figure 1

Schematic representation of the experimental timeline. C57BL/6J mice were exposed to a 5-week Drinking the Dark (DID) procedure. Every 15 days after a 4 h session, a blood sample was obtained from the lateral tail vein to analyze BECs. Concurrently, animals from the EX and EX + EtOH groups were submitted to treadmill exercise training (20 cm/s) for 20 min, 5 days/week. Finally, from pnd 64 to 70, all animals were tested on different behavioral tasks.

Figure 2

Changes in alcohol consumption and weight of the animals during DID protocol. (a) Significant differences were not found between groups, but significant effects of the session (p = 0.001) and week (p < 0.0001) were observed. (b) BEC levels during the first, third, and fifth weeks and animal weight in the different experimental conditions. BECs in the EtOH and EX + EtOH groups are expressed as milligrams per deciliter (mg/dL). The quantity of alcohol in the blood increased over time (p < 0.0001), but significant differences were not found between groups. (c) A significant correlation between BEC levels and EtOH intake in the last 4 h session was found (p < 0.001). (d) Animal weight over time. All data are mean ± SEM.

Figure 3

Behavioral performance in Emotionality and Social preference. (a–d: Elevated-plus maze; e–g: Sucrose splash test; h: The nest building test and representative photographs of nests from the different experimental conditions at 24 h; i,j: Three-chamber test). All data are mean ± SEM, and statistically significant differences were considered when p < 0.05. * Statistical differences between the CON group compared to other groups; + Statistical differences between the EtOH group compared to other groups; statistical differences between the EX group compared to other groups.

Figure 4

Behavioral performance in Spontaneous alternation and exploration/habituation. (a,b: Y-maze; c–j: Open field (exploration); k,l: Open field (habituation). All data are mean ± SEM, and statistically significant differences were considered when p < 0.05. + Represents statistical differences between the EtOH condition compared to other groups.