Serotonin modulates offensive attack in adolescent anabolic steroid-treated hamsters

Chronic anabolic-androgenic steroid (AAS) treatment during adolescence facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study assessed whether adolescent AAS-facilitated offensive attack was modulated by serotonin (5-HT) and if AAS exposure during this developmental period influenced 5-HT innervation to areas of hamster brain implicated in aggressive behavior. In a first experiment, hamsters were administered high-dose AAS throughout adolescence, and then scored for offensive attack following the systemic administration of saline or fluoxetine, a selective 5-HT reuptake inhibitor. Saline-treated hamsters showed high levels of offensive attack, while treatment with fluoxetine attenuated the AAS-facilitated aggressive response. In a second experiment,were administered high-dose AAS or sesame oil throughout adolescence, tested for offensive attack and then examined for differences in 5-HT innervation to areas of the hamster brain important for aggression. Aggressive AAS-treated hamsters showed significant reductions in the number of 5-HT immunoreactive (5-HT-ir) varicosities and fibers in several of these areas, most notably the anterior hypothalamus (AH), ventrolateral hypothalamus (VLH) and medial amygdala (MeA). However, no differences in 5-HT afferent innervation were found in other aggression areas, such as the bed nucleus of the stria terminalis (BNST) and lateral septum (LS). Together, these results support a role for altered 5-HT innervation and function in adolescent AAS-facilitated offensive aggression.