Aquaporin-4 Antagonist Protects Against Acute Alcohol-Induced Behavioral Impairment

Binge drinking rapidly triggers acute neurological dysfunction through direct and indirect effects on the brain. Although widespread, the most affected regions govern planning and decision-making, coordination, and impulse control. Here we suggest that the rapid alcohol induced behavioral impairment is mediated by water transport across the blood brain barrier. Since Aquaporin-4 (AQP4) channels mediate most water transport into the brain, we examined how pharmacologically inhibiting AQP4 affects behavioral output. Thirty-three adult Sprague Dawley rats were placed into 3 conditional groups (saline, ethanol, and A&E). Each group performed the same battery of behavioral assessments. Spatiotemporal recordings of animal behavior were video recorded and analyzed using custom MATLAB scripts. Acute ethanol exposure altered behavioral performance in a task-dependent manner across open field, object recognition, and elevated zero maze assays compared to saline-control trials. Ethanol increased open-field center time (14.92 ± 3.37 vs 2.23 ± 0.79s), object discrimination index (-0.03 ± 0.13 vs 0.51 ± 0.03), and zero-maze open-zone time (293.31 ± 69.60 vs 82.60 ± 19.31s). AQP4 inhibition attenuated the ethanol induced behavioral effects for both the open field test and elevated zero maze by 81.6% and 75.3%, respectively. However, AQP4 inhibition did not protect against ethanol induced impairment for the object recognition test. Our findings suggest that blocking AQP4-mediated water transport may protect against alcohol-induced disruption of context-sensitive risk-guided behavior. Future studies may aim to investigate the extent to which water transport into the brain after alcohol exposure alters the neural activity associated with risk-guided behavioral output.