--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, and Avp 1a and Avp 1b receptors (Oxt, Avpr1a and Avpr1b, respectively) to investigate their specific roles in mediating behavior.? --We have completed a number of studies that confirmed the belief that the Avpr1b would be important in regulating stress responses. In our Avpr1b KO mice, plasma ACTH and CORT levels induced by hypoglycemia are significantly decreased compared with wild-type littermates. In a model of chronic stress, plasma ACTH is decreased when compared with wild-type mice. Our results also suggest that Avpr1b plays a significant role in the HPA axis response to acute immune stress. Dysregulation of the stress response is associated with the pathophysiology of depression, treatment of which with antidepressants involves increasing the availability of monamines at the synaptic cleft. We found that the Avpr1b is required to drive the HPA axis response to acute antidepressant treatment.? --We showed that deficits in Avpr1b and Oxt lead to deficits in female social recognition, but with different consequences. These findings indicate that superficially similar abnormalities in social behavior could have entirely different underlying causes.? --Using our knockout mice, we have shown that a deficit in Oxt leads to reduces prepulse inhibition of the startle reflex, similar to what is seen in schizophrenics. It is possible that administration of an Oxt agonist would be a useful adjunct to commonly prescribed neuroleptics in the treatment of schizophrenia. ? --We have recently created and started studying a conditional KO of the Oxtr. This line has the coding region flanked by special DNA sequences to allow us to temporally and spatially regulate the expression of the Oxtr. Unlike Oxt and total Oxtr KOs, the forebrain KOs are able to lactate and their pups survive. This is allowing us to assess maternal behaviors of the forebrain KO dams as well as the subsequent behaviors of their offspring. We are seeing that this partial reduction in Oxtr leads to subtle deficits in maternal behavior, leading them to be poorer mothers and to be more susceptible to stress. It will be interesting to learn if poor mothering skills in humans are related to deficiencies in Oxt signaling.
Showing the most recent 10 out of 44 publications
