Juvenile social play is a highly rewarding and motivated behavior displayed across mammalian species, including humans, non-human primates, and rats. Social play exposure has been shown to be essential in the development of social skills throughout the lifespan. Autistic children show decreased engagement in social play, which may contribute to lifelong decreases in social competency. Oxytocin (OXT) is a neuropeptide that facilitates the expression of socially rewarding behavior, but the role that OXT plays in the regulation of juvenile social play is still unknown. OXT is primarily produced in the paraventricular nucleus of the hypothalamus (PVN). PVNOXT neurons interact with regions within the brain reward circuitry through direct connections to the nucleus accumbens (NAc), which in turn projects to the ventral pallidum (VP). The PVN, NAc, and VP have all been shown to regulate juvenile social play individually, but whether OXT signaling across these regions is necessary for the expression of social play is unknown. Therefore, I designed three sets of experiments to test the hypothesis that juvenile social play is modulated through this hypothalamic-striatal OXTergic pathway. In aim 1, I used an excitatory DREADD construct to selectively stimulate PVNOXT terminals in the NAc prior to social play exposure. Here, I predicted that chemogenetic stimulation of the PVN-OXT to NAc pathway would increase juvenile social play behavior in both sexes. Although there was no effect of stimulation on social play, I found that chemogenetic stimulation of PVNOXT terminals in the NAc increased social investigation in males and decreased this in females. In aim 2, I determined the effects of chemogenetic inhibition of OXT receptor (OXTR) expressing neurons in the NAc, as well as chemogenetic inhibition of NAcOXTR terminals in the VP on the expression of juvenile social play behavior. As NAc inactivation has been shown to increase juvenile social play behavior, I predicted that chemogenetic inhibition of OXTR-expressing neurons in the NAc and of NAcOXTR terminals in the VP would increase juvenile social play behavior in both sexes. Here, I found that chemogenetic inhibition of the NAcOXTR neurons increased social play behaviors in females but had no effect on male social play behaviors. Additionally, chemogenetic inhibition of the NAcOXTR terminals in the VP had no effect on social play. Lastly, in aim 3, I set out to determine the role of OXT and dopamine (DA) signaling within the NAc. DA plays a vital role in reward and the modulation of motivated behaviors, and DA receptors (DARs) are co-expressed on OXTR neurons in the NAc. Therefore, I hypothesized that both OXT and DA in the NAc modulate the expression of juvenile social play. In detail, I predicted that OXTR agonism would increase social play, while DAR antagonism in the NAc would decrease social play, and would do so in both males and females. Here, I found that OXTR agonism increased female social play behaviors but decreased male social play behaviors. Additionally, DAR-2 antagonism decreased social play in both sexes. However, DAR-1 antagonism had no effect on social play. Together, these studies indicate persistent sex differences mediated by OXT in which NAc-OXT signaling increases female social play behavior but may decrease male social play behavior. These findings could inform clinicians on the potential need for sex-specific OXT-based therapeutics in the treatment of social deficits.
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