Serotonin type 3 receptors stimulate offensive aggression in Syrian hamsters

Abstract

Hamsters repeatedly exposed to cocaine during adolescence display high levels of offensive aggression compared to saline-treated littermates. The escalated offensive phenotype observed in adolescent cocaine-treated animals is modulated by serotonin (5-HT) signaling and can be suppressed by inhibiting 5-HT type 3 receptors, suggesting that these receptors might play an important role in the aggression-stimulating effects of adolescent cocaine exposure. The current study examined this hypothesis and extended earlier studies investigating the relationship between 5HT 3 receptor neural signaling and the offensive response patterns of aggressive, adolescent cocaine-treated animals compared to non-aggressive, saline-treated littermates. Adolescent cocaine-treated hamsters and saline-treated littermates were tested for offensive aggression after the administration of either the 5-HT 3 antagonist 3-tropanylindole-3-carboxylate methiodide (tropisetron) or the 5-HT 3 agonist 1-( m-chlorophenyl)-biguanide hydrochloride (mCPBG). Tropisetron significantly reduced the high levels of offensive responding observed in adolescent cocaine-treated animals, whereas treatment with the 5-HT 3 receptor agonist mCPBG failed to affect the escalated offensive response. Conversely, tropisetron failed to affect very low, baseline levels of aggressive responding seen in adolescent saline-treated animals, while 5-HT 3 receptor activation via mCPBG triggered highly escalated levels of offensive aggression in these animals. Together, these data support a stimulatory role for 5-HT 3 neural signaling in offensive aggression.