μ-Opioid receptors within subregions of the striatum mediate pair bond formation through parallel yet distinct reward mechanisms

Abstract

The prairie vole is a socially monogamous rodent that is an excellent animal model for studies of the neurobiology of social attachment. Such studies have demonstrated that activation of reward circuitry during social interactions facilitates pair bond formation. Within this circuitry, μ-opioid receptors (MORs) modulate naturally rewarding behavior in an anatomically segregated manner; MORs located throughout the striatum (dorsal striatum, NAc core, and the entire NAc shell) are implicated in general motivational processes, whereas those located specifically within the dorsomedial NAc shell mediate positive hedonics (and are referred to as a "hedonic hotspot"). The purpose of the present study was to determine whether MORs within these distinct subregions differentially mediate pair bond formation. We first used receptor autoradiography to compare MOR binding densities between these regions. MOR binding was significantly higher in the NAc core and dorsomedial NAc shell compared with the ventral NAc shell. We next used partner preference testing to determine whether MORs within these subregions differentially mediate pair bonding. Blockade of MORs using 1 or 3 μg of H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 within the dorsal striatum decreased mating during the cohabitation period and inhibited partner preference formation. In contrast, blockade of MORs within dorsomedial NAc shell inhibited partner preference formation without effecting mating behavior, whereas other regions were not involved. Thus, MORs within the dorsal striatum mediate partner preference formation via impairment of mating, whereas those in the dorsomedial NAc shell appear to mediate pair bond formation through the positive hedonics associated with mating.

Figure 1.

MOR binding within the striatum. A, Left, Representative image of MOR binding density within the rostral striatum. B, Right, Representative image of MOR bonding within the caudal striatum. On the right side of each image, we outline the regions analyzed to obtain mean MOR binding density. C, A composite image of the rostral shell of female prairie voles. D, The caudal shell. E, In the rostral striatum, MOR binding was significantly higher in the NAc core and dorsomedial NAc shell compared with the ventral NAc shell (n = 5). F, MOR binding was higher in all regions in the rostral striatum compared with the caudal striatum (n = 5). G, H, There was no difference in MOR binding density between prairie and meadow voles in (G) rostral or (H) caudal regions of the striatum (n = 5). *p ≤ 0.05. **p ≤ 0.005.

Figure 2.

MORs within the dorsal striatum regulate pair bond formation via inhibition of mating. A, Injections of aCSF or the low dose of CTAP into the dorsal striatum did not inhibit partner preference formation, whereas injections of the high dose of CTAP into this region abolished partner preference. Inset, Site of injection shaded in gray (left) and the binding of MOR within the dorsal striatum (right). B–D, MOR blockade did not affect (B) cage time or (C) total contact time (i.e., time spent in contact with the partner + the stranger) during the partner preference test. However, blockade of MORs with the high dose of CTAP decreased the (D) total number of mating bouts during the cohabitation period (n = 6–10). *p ≤ 0.05.

Figure 5.

Diagram images representing injection sites of aCSF, 1 μg CTAP, or 3 μg CTAP into the dorsal striatum, the NAc core, the dorsomedial NAc shell, or the ventral NAc shell.

Figure 3.

MORs within the NAc core do not play a significant role in partner preference formation. A, Neither low nor high dose injections of CTAP into the NAc core impacted partner preference formation. Inset, Site of injection shaded in gray (left) and the binding of MOR within the NAc core (right). B–D, MOR blockade within the NAc did not have an effect on (B) cage time or (C) total contact time (i.e., time spent in contact with the partner + the stranger) during the partner preference test, although there was a trend for a (D) decrease in the number of mating bouts (n = 5 or 6). *p ≤ 0.05 (trend). ^#p = 0.07 (trend).

Figure 4.

MORs within the dorsomedial, but not ventral, NAc shell are important for partner preference formation. A, Site-specific injection of both the low and high dose of CTAP into the dorsomedial NAc shell inhibited partner preference formation, whereas injections of either dose of CTAP were without effect in the ventral NAc shell. Inset, Site of injection into the dorsomedial Nac shell (dark gray) or the ventral NAc shell (light gray) (left) and the binding of MOR within the NAc shell (right). B–D, MOR blockade with either dose of CTAP into the NAc shell did not affect (B) cage time, (C) total contact time (i.e., time spent in contact with the partner + the stranger), or (D) the number of mating bouts (n = 4–9). *p ≤ 0.05. **p ≤ 0.005.