Social instigation and aggressive behavior in mice: role of 5-HT1A and 5-HT1B receptors in the prefrontal cortex

Rationale  Social instigation is used in rodents to induce high levels of aggression, a pattern of behavior with certain parallels to that of violent individuals. This procedure consists of a brief exposure to a provocative stimulus male, before direct confrontation with an intruder. Studies using 5-HT_1A and 5-HT_1B receptor agonists show an effective reduction in aggressive behavior. An important site of action for these drugs is the ventral orbitofrontal cortex (VO PFC), an area of the brain which is particularly relevant in the inhibitory control of aggressive and impulsive behavior. Objectives  The objectives of the study are to assess the anti-aggressive effects of 5-HT_1A and 5-HT_1B agonist receptors [8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT) and CP-93,129] in the VO PFC of socially provoked male mice. To confirm the specificity of the receptor, 5-HT_1A and 5-HT_1B antagonist receptors (WAY-100,635 and SB-224,289) were microinjected into the same area, in order to reverse the agonist effects. Results  8-OH-DPAT (0.56 and 1.0 μg) reduced the frequency of attack bites. The lowest dose of CP-93,129 (0.1 μg) also decreased the number of attack bites and lateral threats. 5-HT1A and 5-HT1B receptor agonists differed in their effects on non-aggressive activities, the former decreasing rearing and grooming, and the latter, increasing these acts. Specific participation of the 1A and 1B receptors was verified by reversal of anti-aggressive effects using selective antagonists WAY-100,635 (10.0 μg) and SB-224,289 (1.0 μg). Conclusions  The decrease in aggressiveness observed with microinjections of 5-HT_1A and 5-HT_1B receptor agonists into the VO PFC of socially provoked mice, supports the hypothesis that activation of these receptors modulates high levels of aggression in a behaviorally specific manner.