Anti-aggressive effects of agonists at 5-HT1B receptors in the dorsal raphe nucleus of mice

Rationale In rodents, serotonin 1B (5-HT1B) agonists specifically reduce aggressive behaviors, including several forms of escalated aggression. One form of escalated aggression is seen in mice that seek the opportunity to attack another mouse by accelerating their responding during a fixed interval (FI) schedule. Responses preceding the opportunity to attack may reflect aggressive motivation. Objective This study investigated the effects of two 5-HT1B receptor agonists on the motivation to fight and the performance of heightened aggression. Materials & Methods Male mice were housed as "residents" and performed nose-poke responses on an FI 10-min schedule with the opportunity to briefly attack an "intruder" serving as the reinforcer. In the first experiment, the 5-HT1B receptor agonist, CP-94,253 (0-10 mg/kg, IP), was given 30 min before the FI 10 schedule. To confirm that CP-94,253 achieved its effects via 5-HT1B receptors, the 5HT(1B/1D) receptor antagonist, GR 127935 (10 mg/kg, IP) was administrated before the agonist injection. In the second experiment, the 5-HT1B agonist CP-93,129 (0-1.0 mu g) was microinjected into the dorsal raphe 10 min before the FI 10 schedule. Results The agonists had similar effects on all behaviors. CP-94,253 and CP-93,129 significantly reduced the escalated aggression towards the intruder at doses lower than those required to affect operant responding. The highest doses of CP-94,253 (10 mg/kg) and CP-93,129 (1.0 mu g) decreased the rate and accelerating pattern of responding during the FI 10 schedule; lower doses were less effective. GR 127935 antagonized CP-94,253's effects on all other behaviors, except response rate. Conclusions These data extend the anti-aggressive effects of 5-HT1B agonists to a type of escalated aggression that is rewarding and further suggest that these effects are associated with actions at 5-HT1B receptors in the dorsal raphe.