After pair-bonding, male prairie voles (Microtus ochrogaster) display aggression toward novel females but not toward their female partner. Here we show that this selective aggression in pair-bonded male prairie voles is associated with increased release of vasopressin (AVP) in the anterior hypothalamus (AH). Pharmacological activation of AVP-V1a receptors (V1aR) in the AH induced selective aggression in sexually naive males, whereas V1aR blockade diminished selective aggression in pair-bonded males. Pair-bonded males also showed an increased density in V1aR binding in the AH compared to their sexually naive counterparts and overexpression of V1aR in the AH, by viral vector-mediated gene transfer, facilitated aggression toward novel females. These data demonstrate that AH-AVP is both necessary and sufficient in the regulation of selective aggression associated with pair-bonding. In the second part of this study, we examined the effects of amphetamine (AMPH) exposure on female-directed aggression and revealed the potential role of AH-AVP underlying this behavior. Repeated AMPH administration in sexually naive male prairie voles enhanced V1aR expression in the AH and induced aggression toward a familiar or unfamiliar female. In addition, this AMPH-induced aggression was blocked by intra-AH administration of a V1aR antagonist. Together, our data reveal a socioneurobiological mechanism, highlighting a critical role of AH-AVP in the regulation of aggression induced by pair-bonding or drug experience in socially monogamous male prairie voles.behavioral pharmacology ͉ drug abuse ͉ microdialysis ͉ neural plasticity ͉ viral-vector gene transfer A ggression is an agonistic behavior that plays an important role for survival and reproductive success. In both vertebrates (1) and invertebrates (2), aggression promotes fitness by acquiring territory, food, and mates, as well as by serving to protect offspring and avoid predation. In humans and nonhuman primates, aggressive behavior operates within social hierarchies to facilitate resource acquisition (3). Among the neurochemicals implicated in aggression (4, 5), arginine vasopressin (AVP), and its homolog vasotocin, have been found to regulate several forms of aggression in numerous species (6, 7) across diverse taxa (8, 9). Even in humans, central AVP correlates with aggressive behavior (10) and mediates anger (11). Therefore, the AVP system may have evolved to be primed by a wide variety of experiences to induce aggression, when appropriate, in social animals (12).Drug use can override neurobiological programs to activate maladaptive forms of agonistic behavior, engaging inappropriate types of physical aggression (13), such as domestic violence (14) and intimate partner homicide (15). As a result, chronic drug abuse can cause permanent neural reorganization (16,17), impairing the adaptive social brain (18), leading to the display of maladaptive social behavior (19). In rodent models such as hamsters, adolescent exposure to cocaine (20) or anabolic steroids (21, 22) induces ag...