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bioRxiv · 10.1101/2025.09.06.674638

The nucleus accumbens to ventral pallidum pathway regulates social play behavior via sex-specific mechanisms in juvenile rats

Lee, J. D. A.·Anderson, D. N.·Orsucci, I. C.·Bowden, S. M.·Veenema, A. H.
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Abstract

Social play behavior is a rewarding behavior predominantly displayed by juveniles of various mammalian species, including humans and rats. Although the mesolimbic reward system is involved in the regulation of social play, how brain regions in this system interact to regulate social play behavior is unknown. Here, we determined the involvement of the ventral pallidum (VP) as well as inputs from the nucleus accumbens (NAc) to the VP in the regulation of social play in male and female juvenile rats. We show that acute pharmacological inactivation of the VP, via microinfusion of the GABA-A receptor agonist muscimol, decreased social play behaviors in both sexes. Next, using Gad1-iCre rats, we show that chemogenetic stimulation of NAcGABA terminals in the VP decreased VP neuronal activation and decreased social play behaviors in both sexes. These findings together indicate that reduced inhibitory NAc input to the VP permits activation of the VP which facilitates the expression of social play behaviors. Lastly, we show that the equal expression of social play behavior in males and females is associated with a female-specific increase in NAc shell activation and a male-specific decrease in activation of the NAc shell neurons projecting to the VP. These sex-specific changes in NAc activity following social play exposure eliminated baseline sex differences in NAc activity. In conclusion, these findings support a model in which the sex-specific modulation of NAc inhibitory input to the VP facilitates activation of the VP that is necessary for the typical and equal expression of social play behavior in male and female juvenile rats.

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Lee, J. D. A., Anderson, D. N., Orsucci, I. C., Bowden, S. M., Veenema, A. H.. 2025-09-13. The nucleus accumbens to ventral pallidum pathway regulates social play behavior via sex-specific mechanisms in juvenile rats. https://doi.org/10.1101/2025.09.06.674638

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