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

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.

Repeated cocaine treatment activates flank marking in adolescent female hamsters.

Cocaine abuse during adolescence represents a significant health risk due to the potential for both acute and long-term negative physical and psychological sequelae, including increased aggressive behavior. This study examined the effect of adolescent cocaine treatment on flank marking (i.e., a stereotypic motor behavior that is part of the response pattern of offensive aggression) in female and male Syrian hamsters (Mesocricetus auratus). Adolescent cocaine treatment activated flank marking in female hamsters when animals were measured upon return to their home cage immediately following drug treatment. Sex differences were observed in cocaine-induced flank marking, as males failed to flank mark when returned to the home cage. In females, the behavioral response was most marked on Day 11 of cocaine treatment in all doses tested. Yet, animals treated with low-dose cocaine (0.5 mg/kg/day) showed the most significant increase in flank marking on and from Day 11 forward as compared to medium- and high-dose cocaine-treated animals and controls. In addition, the response of cocaine-treated animals was vigorous and nearly immediate, as >75% of the flank marks scored were performed within the first 2 min of the behavioral test in >85% of animals examined. Measures of locomotion showed that cocaine had stimulatory effects on motor activity in adolescent female hamsters at all doses tested. Cocaine-treated animals did not differ in body weight gain from controls, suggesting no dramatic physiological effects of adolescent cocaine exposure on body growth at the doses tested.