β-endorphin regulates alcohol consumption induced by exercise restriction in female mice

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.

Sex differences in binge‐like EtOH drinking, corticotropin‐releasing hormone and corticosterone: effects of β‐endorphin

“…We previously observed increased adrenal gland weight in β-E deficient mice following EtOH exposure (Grisel et al 2008;McGonigle et al 2016) but did not explore basal or sex differences. Therefore, immediately following the BT on day 4, the left and right adrenal glands were harvested and total adrenal weight (normalized by body weight, g/kg) was calculated and is summarized in Fig.…”

“…Moreover, CRH signaling in the extended amygdala-comprised the nucleus accumbens shell (NAc), bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA)-mediates binge-like EtOH consumption (Lowery-Gionta et al 2012;Pleil et al 2015;Rinker et al 2017), and we recently observed increased Crh mRNA in the extended amygdala of β-E À/À female mice (McGonigle et al 2016). Therefore, we hypothesized that binge-like drinking is regulated by sex and β-E through alterations in Crh expression and glucocorticoid secretion affecting stress circuitry and anxiety-like behavior.…”

Behavioral and neuronal interactions between exercise and alcohol: Sex and genetic differences

“…During both 2BC and DID, female, but not male, C57BL/6J mice increased their alcohol consumption and preference when their running wheels were locked, again substantiating the idea that female mice may be using wheel running as a substitute for alcohol consumption . Finally, McGonigle et al examined the effect of intermittent wheel access on DID (20% alcohol) using female C57BL/6J, β‐endorphin knock‐out (βE‐KO) and β‐endorphin heterozygote (βE‐HT) mice. Both βE‐KO and βE‐HT significantly increased their alcohol consumption when wheel running was prevented.…”

“…Numerous studies in rodents have provided evidence for an interaction between voluntary wheel running and alcohol consumption . In a recent review, Hallgreen et al pointed out that, “physical exercise is widely regarded as “medicine” for the prevention and treatment of myriad somatic health conditions.” However, the effectiveness of physical activity to treat AUDs remains understudied.…”

“…Another commonly used method to investigate the effect of exercise on alcohol consumption is intermittent wheel access during 2BC and DID alcohol paradigms . For example, McMillan et al reported that initial access to voluntary wheel running decreased 5% and 10% 2BC alcohol consumption in male alcohol‐preferring (P) rats, which were selectively bred for high alcohol consumption, but had no effect on their male nonalcohol‐preferring (NP) counterparts.…”