Variation in oxytocin receptor density in the nucleus accumbens has differential effects on affiliative behaviors in monogamous and polygamous voles

Abstract

Oxytocin receptors in the nucleus accumbens have been implicated in the regulation of alloparental behavior and pair bond formation in the socially monogamous prairie vole. Oxytocin receptor density in the nucleus accumbens is positively correlated with alloparenting in juvenile and adult female prairie voles, and oxytocin receptor antagonist infused into the nucleus accumbens blocks this behavior. Furthermore, prairie voles have higher densities of oxytocin receptors in the accumbens than nonmonogamous rodent species, and blocking accumbal oxytocin receptors prevents mating-induced partner preference formation. Here we used adeno-associated viral vector gene transfer to examine the functional relationship between accumbal oxytocin receptor density and social behavior in prairie and meadow voles. Adult female prairie voles that overexpress oxytocin receptor in the nucleus accumbens displayed accelerated partner preference formation after cohabitation with a male, but did not display enhanced alloparental behavior. However, partner preference was not facilitated in nonmonogamous meadow voles by introducing oxytocin receptor into the nucleus accumbens. These data confirm a role for oxytocin receptor in the accumbens in the regulation of partner preferences in female prairie voles, and suggest that oxytocin receptor expression in the accumbens is not sufficient to promote partner preferences in nonmonogamous species. These data are the first to demonstrate a direct relationship between oxytocin receptor density in the nucleus accumbens and variation in social attachment behaviors. Thus, individual variation in oxytocin receptor expression in the striatum may contribute to natural diversity in social behaviors.

Figure 1.

Alloparental behavior in sham, CMV-GFP, and CMV-OTR female prairie voles. A, There was no effect of treatment on the proportion of females in each treatment group that displayed alloparental behavior. The dark bars represent the percentage of animals that were categorized as alloparental, while the light bars depict the number of females that attacked or ignored the pups. B, The latency to approach pups was not different between groups. C, There was no difference between groups in the amount of time the females spent licking pups, when only the females in each group that displayed alloparental behavior toward the pups were compared. Data are presented as mean ± SEM.

Figure 2.

Mating and partner preference behavior in sham, CMV-GFP, and CMV-OTR female prairie voles. A, B, The latency to first intromission (A) and the number of mating bouts (B) were not significantly different between the groups. C, After a 6 h cohabitation period, none of the groups displayed a significant preference for the partner over the stranger. D, After a cumulative 18 h cohabitation, CMV-OTR-injected females spent significantly more time with the partner than the stranger. The sham- and CMV-GFP-injected females did not spend significantly more time with either male at either time point. E, Scatter plot illustrating the ratio of the time spent with partner/stranger for each individual in the groups. Females spending >67% of their total social contact time with the partner (above the dashed line) are considered to have displayed a partner preference. F, The overall percentage of animals in each group that displayed a partner preference. Data are presented as mean ± SEM. *p < 0.001. n.s., Not significant.

Figure 3.

Analysis of OTR and GFP expression in CMV-OTR and CMV-GFP female prairie voles. OTR density was determined using receptor autoradiography. A, B, There was significant variation in the density of OTR binding in the NAcc of CMV-GFP females. This is in contrast to the prefrontal cortex (PFC), where there is little individual variation in OTR binding density. Scale bar, 1 mm. C, CMV-OTR-injected females had elevated OTR binding in the NAcc relative to controls. D, The dark square surrounding the NAcc depicts the position of the photomicrograph in E. shNAcc, Shell of the NAcc; ac, anterior commissure. E, Photomicrograph (reprinted from Paxinos and Watson, 1998) taken using a 20× objective of GFP-immunoreactivity in the shell of the NAcc of a CMV-GFP female. Immunoreactivity was distributed widely in soma as well as fiber processes. F, Higher-magnification photomicrograph of the image in E illustrating the clear neuronal characteristics of the GFP-immunoreactive cells. Scale bars: E, F, 50 μm.

Figure 4.

Partner preference behavior of female meadow voles after a 24 h cohabitation (A) and after a cumulative 72 h cohabitation (B). CMV-OTR- and CMV-GFP-injected females did not show a partner preference. They spent equal amounts of time with the partner and the stranger at both time points. Data are presented as mean ± SEM.

Figure 5.

Receptor autoradiography illustrating OTR binding density in the NAcc of CMV-GFP (A) and CMV-OTR (B) meadow voles. Note that CMV-GFP female meadow voles had little or no OTR binding in the NAcc. However, OTR binding in the NAcc was dramatically elevated in CMV-OTR female meadow voles. Scale bar, 1 mm.