Atp1a2 contributes modestly to alcohol-related behaviors

Abstract

Atp1a2 has been previously studied for anxiety, learning and motor function disorders, and fear. Since Atp1a2 has been shown to be involved in anxiety and this behavior is a known risk factor for developing alcoholism, we have been investigating Atp1a2 for its potential role in responses to alcohol. This study utilized Atp1a2 knockout mice; Atp1a2 heterozygous mice, with half the amount of protein compared to wild-type mice, were used because Atp1a2 homozygous null mice die shortly after birth. The alcohol-related behavioral experiments performed were loss of righting reflex (LORR), acute alcohol withdrawal measured by handling-induced convulsions (HIC), drinking in the dark (DID), open-field activity (OFA), and elevated plus-maze (EPM). LORR was a 2-day test that measures acute alcohol sensitivity, and rapid and acute functional tolerance (AFT). HIC was a 3-day test to measure alcohol withdrawal, DID was a 4-day test which measures voluntary alcohol consumption, and OFA and EPM measured anxiety with alcohol exposure. The effect of genotype on alcohol metabolism was also examined. There was a genotype effect on rate of alcohol metabolism, but only in males. There was no effect on alcohol withdrawal severity. The Atp1a2 heterozygous mice consumed more alcohol than wild-type mice in the DID test, although only in males. In addition, only males were observed to show rapid tolerance in the LORR test while only female heterozygous mice showed a pretreatment effect on AFT. Alcohol exposure had a greater anxiolytic effect in the heterozygous mice compared to wild-type mice, although, again, there were sex effects with only males showing the effect in OFA and only females in the EPM. Although the behavioral results were mixed, there does appear to be a connection between anxiety and alcohol. Overall, the results suggest that Atp1a2 does contribute to alcohol-related behaviors, although the effect is modest with a clear dependence on sex.

Social and environmental enrichment has different effects on ethanol and sucrose consumption in mice

“…The later model generally involves administering lower concentrations of sucrose to mice for short periods (once weekly or for a few days at a time) (e.g., see Benturquia et al, 2007;Covington, Vialou, LaPlant, Ohnishi, & Nestler, 2011;Ho et al, 2016). However, the DID model generally uses higher sucrose concentrations which are administered for long periods of time (daily for weeks to months) (e.g., see Fritz et al, 2014;Gritz et al, 2016;Patkar et al, 2017). Models utilizing long-term administration of sucrose are not suitable for measuring depression-like behaviors as they produce morphological changes within the brain .…”

“…procedure is most commonly used to model excessive binge-like ethanol consumption in mice for studying the underlying mechanisms of ethanol consumption disorders and identifying potential novel therapeutics (e.g., see Fritz et al, 2014;Gritz, Larson, & Radcliffe, 2016;Patkar et al, 2017). More recently, it has been adapted for studying excessive binge-like sucrose consumption (e.g., see Steensland et al, 2010;Patkar et al, 2017;Dhaher et al, 2009).…”