Anterior hypothalamic vasopressin modulates the aggression-stimulating effects of adolescent cocaine exposure in...

Repeated low-dose cocaine treatment (0.5 mg/kg/day) during adolescence induces offensive aggression in male Syrian hamsters (Mesocricetus auratus). This study examines the hypothesis that adolescent cocaine exposure predisposes hamsters to heightened levels of aggressive behavior by increasing the activity of the anterior hypothalamic-vasopressinergic neural system. In a first experiment, adolescent male hamsters were treated with low-dose cocaine and then scored for offensive aggression in the absence or presence of vasopressin receptor antagonists applied directly to the anterior hypothalamus. Adolescent cocaine-treated hamsters displayed highly escalated offensive aggression that could be reversed by blocking the activity of vasopressin receptors within the anterior hypothalamus. In a second set of experiments, adolescent hamsters were administered low-dose cocaine or vehicle, tested for offensive aggression, and then examined for differences in vasopressin innervation patterns and expression levels in the anterior hypothalamus, as well as the basal- and stimulated-release of vasopressin in this same brain region. Aggressive, adolescent cocaine-treated hamsters showed no differences in vasopressin afferent innervation and/or peptide levels in the anterior hypothalamus compared with non-aggressive, saline-treated littermates. Conversely, significant increases in stimulated, but not basal, vasopressin release were detected from the anterior hypothalamus of aggressive, cocaine-treated animals compared with non-aggressive, saline-treated controls. Together, these data suggest that adolescent cocaine exposure increases aggression by increasing stimulated release of vasopressin in the anterior hypothalamus, providing direct evidence for a causal role of anterior hypothalamic-vasopressin activity in adolescent cocaine-induced offensive aggression. A model for how alterations in anterior hypothalamic-vasopressin neural functioning may facilitate the development of the aggressive phenotype in adolescent-cocaine exposed animals is presented.