Sex differences in vasopressin receptor binding and its role in social memory in rats

Abstract

Sex differences in the regulation of social behavior as well as sex biases in prevalence of social disorders such as autism are likely due to sex differences in brain function. An important candidate for investigating sex-specific regulation of social behavior is the neuropeptide arginine vasopressin (AVP). AVP shows sex differences in synthesis and fiber innervation in the brain, regulates a wide variety of social behaviors, and has been implicated in the etiology of autism. However, a systematic analysis of potential sex differences in AVP receptors in the brain and linking such parameters to sex differences in social behavior is lacking thus far. Therefore, we determined whether there are sex differences in AVP V1a receptor (V1aR) in the rat brain. We then targeted specific brain regions to determine the functional significance of such sex differences. We found that males showed higher V1aR binding densities compared to females in 6 out of 15 forebrain regions analyzed, including the anteroventral thalamic nucleus, hippocampal dentate gyrus, lateral hypothalamus, tuberal lateral hypothalamus, anterior piriform cortex, and stigmoid hypothalamic nucleus. Because of hormonal regulation of the AVP system, we also analyzed differences in V1aR binding due to estrus phase and maternal experience. Since the most robust sex difference in V1aR binding was found in the hippocampal dentate gyrus, we targeted this region to study its functional significance. Surprisingly, not only rats given an injection with a V1aR antagonist, but also vehicle-treated rats failed to show social and object recognition memory. However, social and object investigation times were normal. We therefore hypothesize that the specific impairments in memory function are likely the result of damage to other hippocampal regions due to the cannula placement. Overall, these findings demonstrate that there are significant sex differences in the V1aR in brain regions implicated in social behavior. The functional significance of these sex differences remains to be determined.