Abstract
Animal models have long been used to study the mechanisms underlying the complex association between alcohol and stress. Female mice prevented from running on a home-cage activity wheel increase voluntary ethanol consumption. β-endorphin is an endogenous opioid involved in negatively regulating the stress response and has also been implicated in the risk for excessive drinking. The present study investigates the role of β-endorphin in moderating free-choice consumption of ethanol in response to a blocked activity wheel. Female, transgenic mice with varying levels of the opioid peptide were given daily 2-h access to 20% ethanol with rotations on a running wheel blocked on alternate days. Subjects with low β-endorphin exhibited enhanced stress sensitivity by self-administering larger quantities of ethanol on days when wheel running was prevented. β-endorphin levels did not influence voluntary activity on the running wheel. There were genotypic differences in plasma corticosterone levels as well as corticotropin-releasing hormone mRNA content in multiple brain regions associated with the stress response in these free drinking and running subjects. Susceptibility to stress is enhanced in female mice with low levels of β-endorphin, and better understanding of the role for this opioid in mitigating the response to stressors may aid in the development of interventions and treatments for excessive use of alcohol in women.