Role of Glutamate Receptors in a Mouse Model of Alcohol-Heightened Aggression
Hewage, Nishani B.
- Serotonin is the neurotransmitter most implicated in the neural mechanism of aggressive behavior, including the heightened aggressive behavior that occurs in some individuals after alcohol consumption. Recent data suggest that the glutamate NMDA receptor (NMDAR) may modulate the serotonergic pathway involved in alcohol-heightened aggression. The objective of the present study was to further charac... read moreterize the role of the NMDAR in alcohol-heightened aggression via pharmacological manipulations at the NMDAR in a series of preclinical studies. Male Swiss-Webster mice self-administered 1.0 g/kg (w/v) ethanol and were assessed for aggressive behavior using the resident-intruder paradigm, a translational rodent model of aggression. D-Cycloserine (0-100 mg/kg), ifenprodil (0-10 mg/kg), and amantadine (0-30 mg/kg) were injected intraperitoneally immediately following ethanol self-administration to investigate the effects of manipulations at the NMDAR glycine-binding site, NR2B subunit, and channel pore, respectively. While these compounds did not significantly interact with ethanol to affect aggressive behavior, further investigations are warranted before relegating these sites as irrelevant in alcohol-heightened aggression. Specifically, in a subpopulation of mice characterized as alcohol-heightened aggressors (AHA), ethanol significantly blocked the apparent anti-aggressive effect of D-cycloserine. Furthermore, 17 mg/kg amantadine significantly increased aggressive behavior after ethanol drinking compared to water drinking, and a similar trend was seen after 0.3 mg/kg ifenprodil. Given the individual differences in aggression after alcohol consumption, it would be useful to examine these compounds in a larger population, and particularly in a population of alcohol-heightened aggressors.read less