The role of the NMDA receptor in mediating aggression during withdrawal from ethanol in outbred male mice
Tayeh, Jillian Katherine
2013
- Ethanol withdrawal syndrome, characterized by glutamatergic hyperexcitability in the brain, is a defining characteristic of alcohol dependence. Glutamate hyperexcitability and an upregulation of NMDA receptors have been observed in the brains of mice in withdrawal from ethanol. The present study examined the effects of the uncompetitive NMDA receptor antagonist memantine on aggression during ... read morewithdrawal from ethanol. Outbred Carworth Farm Webster (CFW) male mice were given intermittent, 2-bottle choice access to 20% w/v ethanol and water and aggression during withdrawal periods was assessed after 1-2 and 4-5 weeks of exposure to ethanol. After 16 days of exposure to ethanol, mice drank ethanol in a large range from 25-300 grams/kilogram (g/kg) of body weight. Handling-induced convulsions (HIC) scores were assessed at the end of the 4-5 week testing session to determine withdrawal severity. Neither ethanol-drinking mice nor water-drinking mice reached median HIC scores above 0. During the 1-2 and 4-5 week aggression assessments, memantine was injected (0, 3, 5, 10 mg/kg, i.p.) 8 hours into withdrawal. Memantine did not appear to significantly increase aggression in ethanol-drinking mice but increased aggression in the water-drinking mice at varying doses. For many aggressive behaviors ethanol-drinking and water-drinking mice has significantly different baseline behaviors. These findings suggest that withdrawal appeared to have a depressive affect on aggression in ethanol-drinking mice particularly after 4-5 weeks exposure to ethanol perhaps due to a decrease in extracellular glutamate. Future studies should use microdialysis to determine glutamate levels in the brain in both the withdrawal period as well as during drinking in order to determine if withdrawal or exposure to ethanol is having lasting effects on aggression. It would also be a good idea to use an NMDA receptor agonist to further probe aggressive behavior and see if aggression can be heightened in ethanol-drinking mice after 1-2 and 4-5 week exposure to ethanol.read less
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- 9880w297p
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- tufts:UA005.006.161.00001
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