5-HT3 receptors, alcohol and aggressive behavior in mice

Abstract

Alcohol is a positive modulator at the 5-HT(3) receptor, which has been implicated in alcohol drinking, anxiety and aggression. The reported experiments explored the role of the 5-HT(3) receptor in aggressive behavior and alcohol-heightened aggression. Male, CFW mice were trained to self-administer 1.0 g/kg of alcohol, after which they confronted an intruder. Half of the CFW mice exhibited consistently increased aggressive behavior after alcohol and were designated as showing alcohol-heightened aggression, the others showed no increase and were designated as showing alcohol non-heightened aggression. The 5-HT(3) antagonist, ondansetron (0.01-1.0 mg/kg), significantly reduced aggression in both groups of CFW mice without affecting non-aggressive behaviors. Zacopride also reduced aggression effectively in both groups of mice, but at high doses began to affect walking. Male B6SJL/F2 transgenic 5-HT(3) over-expressing mice (TG) and wild-type mice (WT) were tested for aggressive behavior in their home cage. In those individuals that fought in tests of resident-intruder aggression, no differences were found in aggression after alcohol intake. In tests of aggression without alcohol intake, zacopride reduced aggression in both TG and WT mice at a dose of 56 mg/kg. Antagonism of 5-HT(3) receptors shows promising anti-aggressive effects, although these effects depend on the genetic background of the mice.