SUN-034 - Hypothalamic Oxytocin and Mesolimbic Dopamine Differentially Regulate Sociability and Social Motivation

Reduced social motivation is a core behavioral feature of several neuropsychiatric disorders, including schizophrenia, major depressive disorder, and autism spectrum disorder, and contributes to persistent social withdrawal and loneliness. Oxytocin, a hypothalamic neuropeptide with well-established roles in social behavior, has been investigated as a potential therapeutic for improving social functioning; however, clinical outcomes have been variable. Emerging evidence suggests that oxytocin’s behavioral effects are context-dependent and may differentially influence distinct components of social behavior. Our prior work demonstrates that exogenous oxytocin enhances low-effort sociability while simultaneously reducing social motivation, defined here as the willingness to engage in social interaction when effortful action is required. These divergent effects may arise from interactions between oxytocinergic and dopaminergic systems that differentially regulate social salience and motivational drive.
The present study examines the causal contributions of two key neuroendocrine and motivational nodes, the paraventricular nucleus (PVN) of the hypothalamus and the ventral tegmental area (VTA) to sociability and effort-based social motivation. Male and female C57BL/6J mice received bilateral viral targeting and optical stimulation of either the VTA or PVN. Following recovery, animals completed a behavioral battery designed to dissociate low-effort social engagement from effortful social motivation. Sociability was assessed using the three-chamber social approach test and free dyadic social interaction, while social motivation was measured using two effort-based paradigms developed in our laboratory: a weighted door task and a ladder-climbing task. Additional assays assessed anxiety-like behavior, locomotor function, and social dominance to control for nonspecific effects.
Preliminary findings indicate that activation of VTA circuitry enhances both sociability and effortful social motivation, consistent with a role for dopaminergic signaling in mobilizing social effort. Ongoing experiments are evaluating the effects of PVN activation, with the hypothesis that increased oxytocinergic signaling will preferentially enhance sociability while attenuating effort-dependent social motivation. Together, this work aims to dissociate endocrine and motivational contributions to distinct dimensions of social behavior and to provide mechanistic insight into why oxytocin-based interventions may yield inconsistent outcomes. These findings have implications for the development of more targeted neuroendocrine strategies to address social withdrawal and motivational deficits in clinical populations.

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