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Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice
Published on: January 7, 2019
Mice performance on the staircase test following acute ethanol administration
1Tel Aviv Community Mental Health Center, 9 Hatzvi Street, Ramat Hatayassim, 67197, Tel Aviv, Israel. rweizma@attglobal.net
Pharmacology, Biochemistry, and Behavior
|April 28, 2001
Summary
Ethanol, like diazepam, reduces mouse rearing in a specific test, indicating potential effects on the GABA(A) receptor complex. This action is not blocked by flumazenil, suggesting a unique interaction pathway for ethanol.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- The gamma-aminobutyric acid (GABA(A)) receptor complex is a key target for various psychoactive substances.
- Benzodiazepines are known modulators of GABA(A) receptors, affecting behavior.
- Understanding ethanol's interaction with this complex is crucial for its neurobiological effects.
Purpose of the Study:
- To compare the effects of acute ethanol administration with diazepam on mouse behavior.
- To investigate ethanol's interaction with the GABA(A) receptor complex using the mouse staircase test.
- To assess the role of flumazenil and Ro15-4513 in mediating ethanol's effects.
Main Methods:
- Utilized the mouse staircase test, a validated animal model for assessing benzodiazepine sensitivity.
- Administered acute doses of ethanol and diazepam to mice.
- Observed and quantified rearing events and climbing behavior.
- Tested the effects of flumazenil and Ro15-4513 in conjunction with ethanol.
Main Results:
- Both acute ethanol and diazepam administration significantly reduced rearing behavior in mice.
- This reduction in rearing occurred at doses that did not impair climbing ability.
- The effects of ethanol were insensitive to the benzodiazepine antagonist flumazenil.
- The partial inverse agonist Ro15-4513 did not consistently counteract ethanol's effects on rearing.
Conclusions:
- The mouse staircase test is effective for studying agents acting on the GABA(A) receptor complex, including ethanol.
- Ethanol's reduction of rearing behavior shares similarities with benzodiazepines but may involve distinct mechanisms.
- Ethanol's interaction with the GABA(A) receptor complex is not fully mediated by typical benzodiazepine binding sites.
