Adolescent cocaine exposure and offensive aggression: involvement of serotonin neural signaling and innervation in male Syrian hamsters.
Repeated low-dose cocaine treatment (0.5 mg/kg/day) during adolescence facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study assessed whether adolescent cocaine-facilitated offensive aggression was inhibited by increased serotonin activity and if cocaine exposure during this developmental period influenced serotonin development in the primary aggression areas of hamster brain. In a first experiment, hamsters were treated with low doses of cocaine throughout adolescence and then scored for offensive aggression following the systemic administration of vehicle or fluoxetine, a selective serotonin reuptake inhibitor. Vehicle-treated hamsters showed high levels of offensive aggression, while treatment with fluoxetine inhibited the cocaine-facilitated aggressive response. Only one out of ten fluoxetine-treated animals both attacked and bit intruders, compared to nine out of ten saline-treated animals. In a second experiment, hamsters were administered low doses of cocaine or saline throughout adolescence, tested for offensive aggression, and then examined for differences in serotonin afferent innervation to regions of the hamster brain implicated in aggressive responding. Aggressive cocaine-treated hamsters showed significant reductions (35-50%) in the number of serotonin immunoreactive varicosities and fibers in several aggression areas, including the anterior hypothalamus, lateral septum, medial amygdala, and bed nucleus of the stria terminalis. Together, these results support a role for serotonin innervation and function in adolescent cocaine-facilitated offensive aggression.