Serotonin type-1A receptors modulate adolescent, cocaine-induced offensive aggression in hamsters

Hamsters repeatedly exposed to cocaine throughout adolescence display highly escalated offensive aggression compared to saline-treated littermates. Recently, we have shown that serotonin neural signaling and development play an important role in adolescent cocaine-induced offensive aggression. This study examined whether the adolescent cocaine-induced aggressive response was modulated by serotonin type 1A (5HT1A) receptors. To test this, adolescent male Syrian hamsters were administered cocaine hydrochloride (0.5 mg/kg, i.p.) throughout adolescent development (P27-57) and then tested for offensive aggression after the administration of the 5HT1A receptor agonist R(+)-8-OH-DPAT (0.1, 0.3, 0.6, 1.0, 1.25 mg/kg, i.p.). R(+)-8-OH-DPAT dose-dependently reduced cocaine-induced offensive aggression, with a significant reduction observed at 0.3 mg/kg for most of the offensive responses measured. Animals treated with higher doses of R(+)-8-OH-DPAT (0.6-1.25 mg/kg) prior to testing showed significant reductions in all measures of offensive aggression and social interest towards intruders (i.e., contact time), indicating more general behavioral inhibition. Adolescent cocaine-treated animals did not differ in body weight from controls, suggesting that the increased aggression was not due to increased body mass. These data support a role for 5HT1A signaling in adolescent cocaine-induced aggression.