Rationale: 5-HT(1A) and 5-HT(1B) receptor agonists effectively reduce aggressive behavior in males that has been escalated by social instigation. Important sites of action for these drugs are the receptors in dorsal raphé nuclei (DRN) and the ventral-orbital prefrontal cortex (VO PFC). DRN and VO PFC areas are particularly relevant in the inhibitory control of escalated aggressive and impulsive behavior.
Objectives: The objectives of this study are to assess the anti-aggressive effects of 5-HT(1A) (8-OH-DPAT) and 5-HT(1B) (CP-93,129) receptor agonists microinjected into DRN and VO PFC, respectively, and to study the aggressive behavior in postpartum female Wistar rats using the social instigation protocol to increase aggression.
Methods and results: 8-OH-DPAT (0.56 μg) in the DRN increased aggressive behavior in postpartum female rats. By contrast, CP-93,129 (1.0 μg) microinjected into VO PFC decreased the number of attack bites and lateral threats. 5-HT(1A) and 5-HT(1B) receptor agonists differed in their effects on non-aggressive activities, the former decreasing rearing and grooming and the latter increasing these acts. When 8-OH-DPAT was microinjected into DRN and CP-93,129 was microinjected into VO PFC in female rats at the same time, maternal aggression decreased. Specific participation of 5-HT(1B) receptors was verified by reversal of the anti-aggressive effects using the selective antagonist SB-224,289 (1.0 μg).
Conclusions: The decrease in maternal aggressive behavior after microinjections of 5-HT(1B) receptor agonists into the VO PFC and DRN of female postpartum rats that were instigated socially supports the hypothesis that activation of these receptors modulates high levels of aggression in a behaviorally specific manner, due to activation of 5-HT(1B) receptors at the soma and terminals.