Effects of binge drinking and the anti-inflammatory drug indomethacin on spatial memory and cognitive flexibility in mice

Abstract

In previous research, we found that chronic-intermittent ethanol administration (CIEA), a model of binge drinking, impaired emotional memory in mice, and this impairment was counteracted by the anti-inflammatory drug indomethacin. In the present study, we evaluated the effects of CIEA on spatial memory and cognitive flexibility in adolescent mice of both sexes. Animals were randomly assigned to one of four groups for each sex: SS (saline + saline), SA (saline + alcohol), SI (saline + indomethacin), and AI (alcohol + indomethacin). They were injected with saline, ethanol (3 g/kg) or indomethacin (10 mg/kg) for the first three days of each week, throughout three weeks. 96 h after treatment, subjects learnt a standard water maze task on five consecutive days (4-day training and 1-day probe trial). One day later, mice underwent a reversal task for evaluating spatial cognitive flexibility. Animals receiving alcohol (SA and AI groups) did not differ from controls (SS groups) during the standard task, but animals treated with indomethacin performed better than controls, both in the acquisition trials and the probe trial. During the reversal task, no significant differences between alcohol groups and controls were observed, but the indomethacin group showed significant lower escape latencies than controls. No sex differences were found in either task. In conclusion, binge drinking does not impair spatial memory or spatial cognitive flexibility, while the anti-inflammatory indomethacin improves both, showing that the effects of alcohol and indomethacin on spatial memory (dependent on hippocampus) are different to those they exert on emotional memory (dependent on amygdala).