Anterior hypothalamic vasopressin regulates pair-bonding and drug-induced aggression in a monogamous rodent.

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.