ALCOHOL-HEIGHTENED AGGRESSION IN MICE - ATTENUATION BY 5-HT1A RECEPTOR AGONISTS

One of the critical mechanisms by which alcohol heightens aggression i nvolves forebrain serotonin (5-HT) systems, possibly via actions on 5- HT1A receptors. The present experiments tested the hypothesis that act ivating 5-HT1A receptors by selective agonists will block the aggressi on-heightening effects of ethanol. Initially, the selective antagonist WAY 100635 was used to assess whether or not the changes in aggressiv e behavior after treatment with 8-OH-DPAT and flesinoxan result from a ction at the 5-HT1A receptors. Resident male CFW mice engaged in aggre ssive behavior (i.e. attack bites, sideways threats, tail rattle) duri ng 5-min confrontations with a group-housed intruder male. Quantitativ e analysis of the behavioral repertoire revealed systematic reductions in all salient elements of aggressive behavior after treatment with 8 -OH-DPAT (0.1-0.3 mg/kg, IP) or flesinoxan (0.1-1.0 mg/kg, IP). The 5- HT1A agonists also reduced motor activities such as walking, rearing a nd grooming, although to a lesser degree. Pretreatment with the antago nist WAY 100635 (0.1 mg/kg, IP) shifted the agonist dose-effect curves for behavioral effects to the right. In a further experiment, oral et hanol (1.0 g/kg, PO) increased the frequency of attacks in excess of 2 SD from their mean vehicle level of attacks in 19 out of 76 resident mice. Low doses of 8-OH-DPAT (0.03-0.3 mg/kg) and flesinoxan (0.1, 0.3 , 0.6 mg/kg), given before the ethanol treatment, attenuated the alcoh ol-heightened aggression in a dose-dependent fashion. By contrast, the se low 5-HT1A agonist: doses affected motor activity in ethanol-treate d resident mice to a lesser degree, suggesting behavioral specificity of these anti-aggressive effects. The current results support: the hyp othesized significant: role of 5-HT1A receptors in the aggression-heig htening effects of alcohol. If these effects are in fact due to action at somatodendritic 5-HT1A autoreceptors, then the anti-aggressive eff ects would be associated with decreased 5-HT neurotransmission.