Involvement of ventral pallidal vasopressin in the sex-specific regulation of sociosexual motivation in rats

Abstract

The ventral pallidum (VP) is a critical node of the mesocorticolimbic reward circuit and is known to modulate social behaviors in rodents. Arginine vasopressin (AVP) signaling via the V1A receptor (V1AR) within the VP is necessary for the expression of socially motivated affiliative behaviors in monogamous voles. However, whether the VP-AVP system regulates socially motivated behaviors in non-monogamous species remains unknown. Here, we determined the extent of AVP fiber innervation in the VP as well as the involvement of the VP-AVP system in sociosexual motivation in adult male and female rats. We found that males have nearly twice the density of AVP-immunoreactive (AVP-ir) fibers in the VP compared to females, suggesting the possibility that males experience enhanced AVP signaling in the VP. We further found that this sex difference in VP-AVP-ir fiber density likely arises from an observed sex difference (males > females) in the percentage of VP-projecting AVP-ir cell bodies located in the bed nucleus of the stria terminalis and medial amygdala. To determine the behavioral implications of this sex difference, we next blocked AVP signaling in the VP by antagonizing VP-V1ARs in male and female rats and tested their preference to investigate an unfamiliar male rat or unfamiliar estrus female rat confined to corrals located on opposite ends of a three-chamber apparatus. Under vehicle conditions, males showed a significantly greater innate preference to investigate an opposite sex over same sex conspecific than estrus females. Interestingly, VP-V1AR antagonism significantly reduced males' opposite sex preference, while enhancing estrus females' opposite sex preference. Importantly, all subjects reliably discriminated between male and female stimulus rats regardless of drug treatment, demonstrating a change in motivational state rather than a perceptual impairment induced by VP-V1AR blockade. These results provide a novel functional link between a sex difference in ventral pallidal AVP fiber density and the sex-specific regulation of a sexually motivated behavior necessary for reproductive success.

Structural and functional sex differences in the ventral pallidal vasopressin system are associated with the sex-specific regulation of juvenile social play behavior in rats

“…We report in the current study that juvenile male rats had denser AVP-ir fibers in the VP than juvenile female rats. This is in line with similar sex differences in AVP-ir fiber density in the VP found in adult rats and prairie voles, with males showing denser AVP-ir fibers than females (Lim et al, 2004a; DiBenedictis et al, 2020). The sex difference in AVP-ir fiber density in the VP may be due to sex differences in AVP input to the VP.…”

“…The sex difference in AVP-ir fiber density in the VP may be due to sex differences in AVP input to the VP. In support, in adult rats, AVP input to the VP originates in the BNST and medial amygdala (MeA; DiBenedictis et al, 2020), with adult males having more AVP-ir cells (van Leeuwen et al, 1985; Miller et al, 1989; Wang et al, 1993; DiBenedictis et al, 2017), and a greater percentage of VP-projecting AVP-ir cells (DiBenedictis et al, 2020) than adult females. It would be of interest to determine whether the BNST and MeA also send AVP projections to the VP in juvenile rats, and whether there are sex differences in the strength of these projections.…”

“…One brain structure in the SDMN that is a component of the mesocorticolimbic reward system, and which regulates diverse rewarding and motivating behaviors, is the ventral pallidum (VP; Smith and Berridge, 2005; O’Connell and Hofmann, 2011; Berridge and Kringelbach, 2015). The VP has been implicated in the regulation of rewarding social behaviors, including partner preference in adult prairie voles (Pitkow et al, 2001; Lim and Young, 2004; Lim et al, 2004b) and sociosexual motivation in adult rats (DiBenedictis et al, 2020). Notably, both lines of work indicate an important role of arginine vasopressin (AVP) signaling in the VP for the regulation of these social behaviors.…”

“…For example, blockade of AVP signaling via local bilateral infusion of the vasopressin 1a receptor (V1aR) antagonist in the VP prevented partner preference in monogamous adult male prairie voles (Pitkow et al, 2001; Lim and Young, 2004), while viral vector-mediated overexpression of V1aR in the VP induced a partner preference in non-monogamous adult male meadow voles (Lim et al, 2004b). Furthermore, blockade of AVP signaling in the VP decreased investigation of the opposite sex in adult male rats, while it increased investigation of the opposite sex in adult female rats (DiBenedictis et al, 2020). This latter study highlights a sex-specific role of AVP signaling in the VP in the regulation of adult social behaviors.…”

The Social versus Food Preference Test: A behavioral paradigm for studying competing motivated behaviors in rodents

“…In our adaptation of this paradigm, we examined social versus food preference using a three-chamber apparatus where the social stimulus and the food stimulus were placed on opposite ends (Fig 1) [2]. This con guration allows for a neutral middle chamber zone instead of a forced choice that two-chamber con gurations elicit, and its use was based on our previous experiences with social novelty preference [3] and opposite sex preference [4] tests in rats, and well-characterized sociability and social novelty preference tests in mice [5].…”