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.