Investigating the role of oxytocin signaling in the social regulation of eating

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Project Summary/Abstract Oxytocin is an evolutionarily conserved neuropeptide primarily produced and secreted from the paraventricular and supraoptic nuclei of the hypothalamus. Widespread expression of the oxytocin receptor (OXTR) across various brain regions allows oxytocin to mediate a wide range of effects on behavior. Though classically known for its functions in mediating social and maternal behavior, a growing body of evidence from both animal models and human studies indicates that the neuropeptide oxytocin is a potent anorexigenic signal and a promising target for obesity pharmacotherapy development [1-4]. Indeed, intranasal oxytocin for weight loss is currently under investigation in an active clinical trial [5]. The interest in the oxytocin system as a target for obesity treatment is based, in part, on findings showing that intranasal oxytocin reduces intake of palatable foods in humans [6], and that these effects are more potent in participants with obesity [7]. A deeper understanding of the neural pathways and behavioral processes mediating oxytocin's effects on food intake and food-motivated behavior is imperative given the clinical potential for this system. Oxytocin has been most widely studied for its influence on social behavior. Food intake regulation is heavily influenced by social factors in both humans and rodents, yet the extent that oxytocin's influence on these two related fundamental behaviors is interconnected has not been previously investigated. Further, many of the behaviors modulated by oxytocin show sexual dimorphism, including both social behaviors and food intake control [8, 9]. Here we focus on the dorsal hippocampus (HPCd) as a candidate brain region where these functions overlap as HPCd oxytocin signaling facilitates social memory in sexually dimorphic ways [10] and this region has been recently linked to food intake control [11]. Our preliminary results show that HPCd oxytocin delivery in male rats reduces intake when isolated in the home cage, yet increases food intake in the presence of a familiar, but not an unfamiliar conspecific. Aim 1 experiments build off these findings using a novel social eating paradigm and both pharmacological and virogenetic approaches in males and females to investigate how HPCd OXTR signaling modulates food intake in social context- and sex-specific ways. Our additional preliminary data reveal that central oxytocin enhances social transmission of food preference (STFP) learning in a conspecific familiarity-dependent manner. A recent paper identified a role for the HPCd in mediating STFP learning through dopamine signaling [12]. Aim 2 experiments will build off these findings to investigate whether the HPCd is a site of action mediating oxytocin's effects on STFP (Aim 2), and will utilize pharmacological, neuroanatomical, and in vivo imaging strategy to assess the extent to which oxytocin and dopamine systems interact to regulate eating in a social context- and sex-dependent manner (Aim 3). Collectively, these experiments will reveal novel neural, physiological, and behavioral mechanisms mediating oxytocin's effects on food intake control.