3α-hydroxy-5α-pregnan-20-one: Alcohol Consumption and Anxiety in GABAA α2 knock-in C57Bl/6 Mice
Gunner, Georgia
2012
- Allopregnanolone has demonstrated anxiolytic and anticonvulsant properties via a GABAergic mechanism of action similar to that of benzodiazepines. Intermittent exposure to ethanol has produced high levels of alcohol consumption in the C57Bl/6 mice strain (Hwa et al., 2011). Withdrawal from alcohol produces anxiogenic effects in many species. A possible synergist action for ethanol and the endogenous ... read moreneurosteroid allopregnanolone may exist at the GABAA receptor. Male and female mutant C57Bl/6 GABAA ��2 knock-in allopregnanolone insensitive mutants were subjected to the intermittent access protocol for eight weeks and then analyzed for severity of alcohol withdrawal using the Handling Induced Convulsion (HIC) score (Goldstein, 1972). Animals were tested for anxiety-like behaviors during ethanol withdrawal in the open field and social preference tests after injections of 5.0 mg/kg and 10.0 mg/kg allopregnanolone and 0.56 mg/kg midazolam. There were no main effects for increased anxiolytic behaviors across genotypes post allopregnanolone and midazolam injection; however main effects for sex and ethanol withdrawal were discovered. Male animals and ethanol na��ve animals displayed less anxiety-like behaviors in the social preference and open field tests, regardless of drug treatment. This study suggests that ethanol and allopregnanolone behavioral effects are mediated through a similar neural pathway that is likely to be related to action at the GABA-A receptor.read less
- ID:
- 3b591m615
- Component ID:
- tufts:UA005.006.151.00001
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