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Updated: Mar 30, 2026
Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder
Published on: June 23, 2023
BK Channel β1 Subunit Contributes to Behavioral Adaptations Elicited by Chronic Intermittent Ethanol Exposure
Max Kreifeldt1, Chelsea Cates-Gatto2, Amanda J Roberts2
1Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California.
Background:
Large conductance, calcium- and voltage-activated potassium (BK) channels regulate neuronal excitability and neurotransmission. They can be directly activated by ethanol (EtOH) and they may be implicated in EtOH dependence. In this study, we sought to determine the influence of the auxiliary β1 and β4 subunits on EtOH metabolism, acute sensitivity to EtOH intoxication, acute functional tolerance, chronic tolerance, and handling-induced convulsions during withdrawal.
Methods:
Motor coordination, righting reflex, and body temperature were evaluated in BK β1 and β4 knockout, heterozygous, and wild-type mice following acute EtOH administration. Chronic tolerance and physical dependence were induced by chronic intermittent inhalation of EtOH vapor.
Results:
Constitutive deficiency in BK β1 or β4 subunits did not alter the clearance rate of EtOH, acute sensitivity to EtOH-induced ataxia, sedation, and hypothermia, nor acute functional tolerance to ataxia. BK β1 deletion reduced chronic tolerance to sedation and abolished chronic tolerance to hypothermia, while BK β4 deletion did not affect these adaptations to chronic EtOH exposure. Finally, the absence of BK β1 accelerated the appearance, while the absence of BK β4 delayed the resolution, of the hyperexcitable state associated with EtOH withdrawal.
Conclusions:
Altogether, the present findings reveal the critical role of BK β1 in behavioral adaptations to prolonged, repeated EtOH intoxication.
