1. ¹Center for Behavioral Neuroscience, Department of Psychiatry, Emory University, Atlanta, GA, USA
2. ²Clinical Neuroendocrinology Branch, National Institute of Mental Health, NIH, Bethesda, MD, USA
3. ³Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA

Correspondence: IF Bielsky, Yerkes National Primate Research Center, 954 Gatewood Drive, Atlanta, GA 30329, USA. Tel: +1 404 727 8269; Fax: +1 404 727 8070; E-mail: irapopo@emory.edu

Received 16 July 2003; Revised 23 October 2003; Accepted 28 October 2003; Published online 26 November 2003.

Abstract

Considerable evidence suggests that arginine vasopressin (AVP) is critically involved in the regulation of many social and nonsocial behaviors, including emotionality. The existence of two AVP receptors in the brain, namely the V1a and V1b subtypes, and the lack of clear pharmacological data using selective agonists or antagonists, make it difficult to determine which receptor is responsible for the AVP-mediated effects on behavior. Here we report the behavioral effects of a null mutation in the V1a receptor (V1aR) in male mice. Male mice lacking functional V1aR (V1aRKO) exhibit markedly reduced anxiety-like behavior and a profound impairment in social recognition. V1aRKO performed normally on spatial and nonsocial olfactory learning and memory tasks. Acute central administration of AVP robustly stimulated stereotypical scratching and autogrooming in wild-type (WT), but not V1aRKO males. AVP and oxytocin (OT) mRNA and OT receptor-binding levels were similar in WT and V1aRKO mice. Given the current findings, the V1aR may provide a novel potential pharmacological target for social and affective disorders including autism, and anxiety disorders.