TY - JOUR T1 - Ethanol’s action at BK channels accelerates the transition from moderate to excessive alcohol consumption JF - bioRxiv DO - 10.1101/2020.10.29.360107 SP - 2020.10.29.360107 AU - Agbonlahor Okhuarobo AU - Max Kreifeldt AU - Pushpita Bhattacharyya AU - Alex M Dopico AU - Amanda J Roberts AU - Gregg E Homanics AU - Candice Contet Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/11/30/2020.10.29.360107.abstract N2 - Large conductance potassium (BK) channels are among the most sensitive molecular targets of ethanol. Whether the action of ethanol at BK channels influences the motivation to drink alcohol remains to be determined. In the present study, we sought to investigate the behavioral relevance of this interaction by introducing in the mouse genome a point mutation (BK α K361N) known to render BK channels insensitive to ethanol while preserving their physiological function. We demonstrate that preventing ethanol’s interaction with BK channels at this site hinders the escalation of voluntary alcohol intake induced by repeated cycles of alcohol intoxication and withdrawal. In contrast, the mutation does not alter ethanol’s acute behavioral effects, nor the metabolic and activity changes induced by chronic exposure to alcohol. Our findings point at BK channel ethanol-sensing capacity as a vulnerability mechanism in the transition from moderate alcohol consumption to pathological patterns of alcohol abuse.Competing Interest StatementThe authors have declared no competing interest. ER -