Atp1a2 contributes modestly to alcohol-related behaviors.
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.
Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: smgritz@gmail.com.
Stephanie M
SM
Gritz
Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: Colin.Larson@ucdenver.edu.
Colin
C
Larson
Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80301, USA. Electronic address: Richard.Radcliffe@ucdenver.edu.
Richard A
RA
Radcliffe
D000428:Alcohol Drinking / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057897:Reflex, Righting / Q000187:drug effects / Q000502:physiology*; D012737:Sex Factors; D000254:Sodium-Potassium-Exchanging ATPase / Q000172:deficiency / Q000378:metabolism*
D000431:Ethanol; C401838:Atp1a2 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase
ATP1A2; Alcohol; Anxiety; Behavior; Heterozygous mouse