Serotonin type 3 receptors modulate the aggression-stimulating effects of adolescent cocaine exposure in Syrian hamsters (Mesocricetus auratus).

Repeated cocaine (0.5 mg/kg) exposure throughout adolescence stimulates offensive aggression in hamsters. These studies examined whether the cocaine-induced aggressive response was regulated by serotonin Type 3 (5-HT(3)) receptor activity and correlated with altered 5-HT(3) receptor expression. Cocaine-treated Syrian hamsters (Mesocricetus auratus) were tested for aggression after the administration of either the 5-HT(3) antagonist 3-tropanylindole-3-carboxylate methiodide (tropisetron; 0.01-1.20 mg/kg) or the 5-HT(3) agonist l-(m-chlorophenyl)-biguanide hydrochloride (mCPBG; 5.0-15.0 mg/kg), alone or in combination. Tropisetron alone dose dependently reduced cocaine-induced aggression, with a significant reduction at 0.3 mg/kg, whereas mCPBG was ineffective. mCPBG administered prior to tropisetron required a higher dose (1.2 mg/kg) of antagonist to block aggression, indicating a selective 5-HT(3) effect. Cocaine-treated hamsters showed altered 5-HT-sub-3 immunoreactivity in several brain areas implicated in aggression control. These data support a role for 5-HT(3) receptors in adolescent cocaine-induced aggression.