Activation of μ-Opioid Receptors in the Dorsal Striatum is Necessary for Adult Social Attachment in Monogamous Prairie Voles

Abstract

Despite significant evidence that opioids are involved in attachment by mediating social reward and motivation, the role of opioids in the formation of adult social attachments has not been explored. We used the socially monogamous prairie vole (Microtus ochrogaster) to explore the role of endogenous opioids in social bonding by examining partner preference formation in female prairie voles. We hypothesized that m-opioid receptors (MORs) in the striatum have a critical role in partner preference formation. We therefore predicted that peripheral administration of an opioid receptor antagonist would inhibit partner preference formation, and more specifically, that m-opioid selective receptor blockade within the striatum would inhibit partner preference formation. To test our hypotheses, we first administered the non-selective opioid antagonist naltrexone peripherally to females during an 18-h cohabitation with a male and later tested the female with a partner preference test (PPT). Females showed a dose schedule-dependent decrease in partner preference in the PPT, with females in the continuous dose group displaying stranger preferences. Next, we administered microinjections of the MOR selective antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) into either the nucleus accumbens shell (NAS) or the caudate-putamen (CP) immediately before a 24-h cohabitation with a male, and later tested the female with a PPT. Females receiving CTAP into the CP, but not the NAS, showed no preference in the PPT, indicating an inhibition of partner preference formation. We show here for the first time that MORs modulate partner preference formation in female prairie voles by acting in the CP.

κ-Opioid Receptors within the Nucleus Accumbens Shell Mediate Pair Bond Maintenance

“…A previous study provided a very cursory initial description of -opioid receptor distributions for prairie voles (Insel and Shapiro, 1992), and a more recent study described the distribution of -opioid receptors within the striatum (Burkett et al, 2011). Here, we significantly extend these previous findings by providing the first description of -opioid receptor binding throughout the prairie vole brain (Fig.…”

“…In contrast to negative affective states induced by -opioid-receptor blockade, activation of these receptors is associated with positive hedonics and mediates the rewarding properties of positive social incentives such as play and contact comfort (Panksepp et al, 1980;Vanderschuren et al, 1995;Trezza et al, 2011). Moreover, activation of -opioid receptors is important for the early stages of pair bond formation, as blockade of these receptors within the striatum inhibits the formation of a partner preference (Burkett et al, 2011). This is especially interesting given the relationship between -opioid receptors and D 2 -like receptors, which also facilitate pair bond formation (Gingrich et al, 2000;Aragona et al, 2006).…”

“…To ultimately identify the central location of -opioid receptor regulation of selective aggression, it was first necessary to determine the distribution of opioid receptors within prairie vole brains. Since very limited knowledge exists with respect to opioid receptor distributions in the vole brain (Insel and Shapiro, 1992;Burkett et al, 2011), we conducted a detailed analysis of -and -opioid receptor binding for this species.…”

Gene expression correlates of social evolution in coral reef butterflyfishes

“…Preliminary investigations suggest that opioid and/or MOR action within mesolimbic reward system also mediates reward processing in teleosts 76,77 . In prairie voles in particular, the mu-opioid system plays a critical role in facilitating pair bond formation [35][36][37] . Its effects are exerted within striatal regions of the brain, including the dorsal striatum, dorsomedial NAcc shell, and caudate putamen [35][36][37] ; where dorsal striatum MORs are believed to facilitate pair bond formation by promoting mating during CPP, and dorsomedial MORs are believed to do so by modulating the positive hedonics of mating during CPP 36 .…”

“…As with dopamine, different opioid receptor sub-types appear to selectively mediate either pair bond formation or maintenance. Specifically, mu-opioid receptors (MORs) within sub-structures of the striatum (ie., the caudate putamen (CP), dorsal striatum, and dorsomedial NAcc shell) regulates pair bond formation 35,36 . Dorsal striatum MORs achieve this through regulating mating, while dorsomedial NAcc shell MORs appear to achieve this through mediating positive hedonics associated with mating 36 .…”