β-Endorphin influences sedative and ataxic effects of alcohol

Abstract

Beta-endorphin (β-E) is an opioid peptide linked to the behavioral effects of ethanol. For example, β-E provides negative feedback to inhibit the hypothalamic-pituitary-adrenal (HPA) stress axis, and neuroadaptation of this system to ethanol may facilitate sex differences in disordered drinking. Locomotor sensitivity to ethanol may also influence the risk for addiction; however, the role of β-E in psychomotor effects of ethanol is not fully understood. We examined the role of β-E and sex on locomotor effects of ethanol using adult male and female wild-type C57BL/6J and β-E deficient B6.129S2-Pomctm1Low/J mice in a parallel rod floor apparatus following 0.75 or 2.0 g/kg ethanol. Beginning 15 min after intraperitoneal injection, we recorded foot slips, distance traveled, slips per meter, first instance of immobility, and total time spent off-balance (lying on the floor) over 15 min, and collected blood for analysis of ethanol concentration 60 min after injection. Overall, β-E deficient mice were more sedated and ataxic following ethanol; at the lower dose they slipped more frequently and had a higher rate of slips per meter traveled. At the higher dose, β-E deficient mice were predominantly sedated, slipping less frequently, and traveling less, as well as spending more time off-balance and becoming immobile sooner. Genotype interacted with sex in that male β-E deficient mice slipped more frequently than their female counterparts, suggesting that β-E may elicit sex-dependent effects of ethanol-induced ataxia. Blood ethanol concentration did not differ between any group, suggesting that behavioral differences result from altered sensitivity to ethanol. Our data support the contention that β-E modulates the locomotor effects of ethanol and may influence ataxia in a sex-dependent manner. These findings help elucidate the role of β-E in diverging behavioral responses to ethanol and may aid the development of targeted treatments for alcohol use disorders.