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. 2025 Aug:174:105792.
doi: 10.1016/j.yhbeh.2025.105792. Epub 2025 Jul 26.

Sex difference in the effects of ventral pallidum vasopressin 1a receptor partial knockdown on social behavior in mice

Affiliations

Sex difference in the effects of ventral pallidum vasopressin 1a receptor partial knockdown on social behavior in mice

Caitlin N Friesen et al. Horm Behav. 2025 Aug.

Abstract

The neuropeptide vasopressin (AVP) regulates a diverse array of social behaviors, often having different functions in males and females. This sex difference is due, in part, to the AVP cells in the bed nucleus of the stria terminalis (BNST), which are more numerous in males than in females. These AVP cells send stronger projections to several brain regions that express the vasopressin 1a receptor (V1aR), including the ventral pallidum (vPal), an area broadly implicated in reward-seeking behavior. Previous experiments manipulating V1aR in vPal have found that activation of V1aR in this area mediates AVP effects on social behavior with differential effects on male and female rats across different social contexts. Consequently, to better understand the role of V1aR in vPal, we reduced V1aR expression in the vPal using a viral-mediated RNA-interference approach in male and female mice and tested their social investigatory, aggressive, copulatory and communicative responses to male and female conspecifics as well as their responses to anxiogenic or rewarding stimuli. Partial knockdown of V1aR in vPal of males reduced their social investigation of other males, but not of females, whereas the same manipulation had no effect on social investigation in females. In addition, partial knockdown in males reduced latencies to ejaculate during copulation. Reduction in V1aR within vPal did not influence communicative and aggressive behaviors, urine investigation, anxiety-like behavior, or sucrose preference. These results suggest that V1aR activity in the vPal specifically facilitates intermale investigation in adult mice but normally dampens their ejaculatory behavior.

Keywords: Communication; Copulation; Sex differences; Social behavior; Social investigation; Vasopressin; Vasopressin receptor.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aras Petrulis reports financial support was provided by National Institute of Mental Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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