Antiaggresive and anxiolytic effects of gepirone in mice, and their attenuation by WAY 100635

The purpose of the investigation was to ascertain whether (a) the antiaggressive effects of the 5-HT1A partial agonist, Gepirone, could be mediated via its anxiolytic action; (b) the selective 5-HT1A antagonist, WAY 100635, reversed these effects, and (c) the modulation of "stress hyperthermia" could be attributed to direct effects of the drugs. Isolated male mice were treated with WAY 100635 (0, 1.5, 2.5, and 5 mg/kg) given 15 min prior to Gepirone (0, 2.5, 5, and 7.5 mg/kg). Rectal temperature was taken before the first injection and again prior to the behavioral tests. In the first session only, subjects were tested for anxiety on the elevated plus-maze before the resident-intruder test. Gepirone reduced aggression in a dose-dependent manner. This effect was counteracted by all doses of WAY 100635. On the elevated plus maze, Gepirone increased open-arm entries and duration and reduced risk assessment. The largest dose of WAY 100635 had a mild direct anxiolytic action, but all doses reduced the anxiolytic action of the largest dose of Gepirone. Body temperature was decreased dose dependently by Gepirone, an effect prevented by WAY 100635. The results justify attributing the involvement of the 5-HT1A receptors in the modulation of aggression and anxiety.