β‐Endorphin Mediates Behavioral Despair and the Effect of Ethanol on the Tail Suspension Test in Mice

Abstract

Background The opioid peptide β-Endorphin (β-E) is synthesized and released in response to stressful stimuli as well as acute alcohol administration. The release of β-E following exposure to an inescapable aversive situation may mediate behaviors that contribute to allostasis of the stress response. The present study examines the effects of β-E on immobility in assays involving inescapable stress, both under basal conditions as well as after acute administration of EtOH. Methods Female and male transgenic mice with varying capacities to translate β-E were subject to either the forced swim (FST, Experiment 1) or tail suspension test (TST, Experiment 2). In Experiment 3, mice were divided into three groups based on hormonal status (male, female-estrous and female-nonestrous) and injected with either 1 g/kg EtOH or equivolume saline 14 min prior to behavioral assessment on the TST. Results Experiments 1 and 2 demonstrated a direct relationship between β-E levels and immobility. There were also sex differences in behavior in these tests, with males displaying more immobility than females. A main effect of genotype in Experiment 3 replicated findings in Exp 1 & 2. There was also an effect of EtOH (increasing immobility) and a significant interaction reflecting a particularly robust effect of the drug in mice with low β-E. In addition, there were interactions between β-E, EtOH effects and hormonal status. Conclusions These findings support the contention that β-E moderates behavioral responses to stressful stimuli and suggest a role for this peptide in coping behavior. Furthermore, the effects of EtOH on the response to stress may be mediated by β-E. Sex differences in this influence may contribute to sex differences in disease susceptibility and expression.

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

“…However, Zhou et al (2017) did not see an effect of pituitary-specific POMC knockout on drinking in the DID model. Variations in β-E also influence anxiety-like behavior sex-dependently, as β-E À/À female mice display heightened stress responses relative to other groups (Grisel et al 2008;Barfield et al 2010;Barfield et al 2013). In the present study, we demonstrate that β-E À/À female mice also exhibit approximately two to threefold increases in plasma CORT and Crh mRNA in the BNST and CeA compared with wild-type female mice.…”

“…There was a main effect of sex (female mice > male mice), and a sex by genotype interaction with post hoc analysis indicating that β-E À/À female mice consumed more EtOH overall than β-E +/À and β-E +/+ female and β-E À/À male mice. Data are presented as means ± SEM; *P < 0.05 (Bonferroni corrected); n for each group are displayed within their respective bar these lines (Grisel et al 2008;Barfield et al 2010;Barfield et al 2013), but in order to assess the behavioral relevance of the physiological changes in endocrine measures, we tested a separate group containing only female +/+ and À/À mice for anxiety-like behavior in the LDB after the 4-day DID procedure. Linear regression revealed a significant relationship between BECs and preference for the light side of a LDB in β-E À/À female mice (F (1,8) = 12.02, P = 0.0085, R 2 = 0.60), but not β-E +/+ female mice (F (1,5) = 0.008, P = 0.93), supporting the contention that β-E À/À female mice exhibit heightened sensitivity to the anxiolytic effects of EtOH (Fig.…”

“…β-Endorphin also regulates hypothalamic-pituitaryadrenal axis (HPA-axis) activity via μ-opioid mediated inhibition (Buckingham 1986;Wynne & Sarkar 2013), influences basal anxiety-like behavior and EtOH-mediated anxiolysis (Grisel et al 2008;Barfield et al 2010;Barfield et al 2013), and interacts with CRH in brain regions associated with stress and anxiety (Reyes et al 2006;Lam & Gianoulakis 2011). 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).…”

Reduced Tissue Levels of Noradrenaline Are Associated with Behavioral Phenotypes of the TgCRND8 Mouse Model of Alzheimer's Disease

“…The stress of i.p. injections may have influenced latency scores, as has been reported previously (Barfield et al, 2010). Thus, duration of immobility is deemed the most reliable readout of the tail suspension test (Cryan et al, 2005).…”

&beta;-Endorphin and Alcoholism

“…In β-endorphin deficient animals, stress response to EtOH becomes increasingly more hormone dependent (Barfield et al, 2010). In addition to main effects of both sex and β-endorphin on measures of stressinduced behavior, the effect of EtOH was most profound in females deficient in endorphin.…”