The role of glutamate via the NMDA receptor in aggressive behavior after ethanol consumption in mice
Bahamon, Brittany N.
- Alcohol has been linked to two-thirds of violence in humans (Krug et al., 2002). However, only certain individuals are more likely than others to engage in aggressive behavior after drinking (Cloninger, 1987). Mice that display more than two standard deviations of aggressive behavior after ethanol drinking compared to water drinking can be considered alcohol-heightened aggressive (AHA) mice (Micze... read morek et al., 1998) and are clinically relevant models. Serotonergic projections from the dorsal raphe nucleus (DRN) to the prefrontal cortex (PFC) are involved in modulation of aggression. Because the N-Methyl-d-aspartate receptor (NMDAR) has been implicated in ethanol-associated phenomena such as tolerance, dependence, withdrawal, craving, and relapse (Trujillo et al., 1995; Krystal et al., 2003, this study sought to examine the role of glutamate via the NMDAR in alcohol-heightened aggression in mice. Because ethanol antagonizes the NMDAR (Lovinger et al., 1989; Follesa & Ticku, 1996; Kumari & Ticku, 1998; Roberto et al., 2004; Qiang & Ticku, 2005), researchers expected an increase in aggressive behavior after alcohol consumption. Male CFW mice were trained to self-administer 1 g/kg of 6% EtOH or the equivalent volume of water. In the first experiment, mice were systemically injected with memantine (1,3,10,17 mg/kg) immediately after drinking and then confronted with an intruder mouse in the home cage. Aggressive behavior significantly increased at the lower doses of memantine (1 and 3 mg/kg) after ethanol but not water consumption. In the second experiment, mice were microinjected with AP-5 (0.1,1μg) in the DRN. There was a significant drug effect in AHA animals but not in ANA animals. This study suggests that glutamate specifically via the NMDAR may have a role in regulating alcohol-heightened aggression in mice; however, this role may not be limited to the NMDAR or the DRN.read less