Vasopressin (Avp) and oxytocin (Oxt) are neurohormones that are best known for their peripheral actions in regulating salt and water balance, blood pressure, lactation and parturition. However, numerous pharmacological studies have implicated these hormones in various behaviors as well, including aggressive, affiliative, and maternal. We have made gene knockouts (KO) for the mouse Oxt, Avp 1a and Avp 1b receptors (Oxt, Avpr1a and Avpr1b, respectively) to investigate their specific roles in mediating behavior. We made the Avpr1b KO first as its CNS role was at that time completely unknown. We found that the Avpr1b KO has a marked decrease in social aggression, including maternal, but not predatory. Furthermore, the offensive retaliatory component of defensive behavior is lacking, but not the protective aspects, leading to differences in hierarchy characteristics. The mice also have deficits in social recognition and motivation in the presence of normal olfactory acuity and memory. In contrast, we observed relatively minor deficits in the Avpr1a KOs. These mice have a slightly longer circadian tau (length of the day in constant darkness). They also have significant deficits in olfaction but, surprisingly, not in aggression, social recognition, or anxiety- and depression-related behaviors. Neither VP receptor appears to influence the acute toxic effects of alcohol. Finally, we have recently created and started studying a conditional KO of the Oxtr. This line has the coding region flanked by LoxP sites and will allow us to temporally and spatially regulate the expression of the Oxtr. We have initially generated total and postnatal day 14 forebrain knockouts. Unlike Oxt and total Oxtr KOs, the forebrain KOs are able to lactate and their pups survive. This will allow us to assess maternal behaviors of the forebrain KO dams as well as the subsequent behaviors of their offspring.
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