The prairie vole is a socially monogamous species in which breeder pairs typically show strong and selective pair bonds. The establishment of a pair bond is associated with a behavioral transition from general affiliation to aggressive rejection of novel conspecifics. This "selective aggression" is indicative of mate guarding that is necessary to maintain the initial pair bond. In the laboratory, the neurobiology of this behavior is studied using resident-intruder testing. Although it is well established that social behaviors in other species are mediated by endogenous opioid systems, opiate regulation of pair bond maintenance has never been studied. Here, we used resident-intruder testing to determine whether endogenous opioids within brain motivational circuitry mediate selective aggression in prairie voles. We first show that peripheral blockade of -opioid receptors with the antagonist norbinaltorphimine (nor-BNI; 100 mg/kg), but not with the preferential -opioid receptor antagonist naloxone (1, 10, or 30 mg/kg), decreased selective aggression in males. We then provide the first comprehensive characterization of -and -opioid receptors in the prairie vole brain. Finally, we demonstrate that blockade of -opioid receptors (500 ng nor-BNI) within the nucleus accumbens (NAc) shell abolishes selective aggression in both sexes, but blockade of these receptors within the NAc core enhances this behavior specifically in females. Blockade of -opioid receptors within the ventral pallidum or -opioid receptors with the specific -opioid receptor antagonist H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-PenThr-NH2 (1 ng CTAP) within the NAc shell had no effect in either sex. Thus, -opioid receptors within the NAc shell mediate aversive social motivation that is critical for pair bond maintenance.

The monogamous prairie vole displays developmental sensitivity to early pharmacological manipulation in a number of species-typical social behaviors. The long-term consequences of altering the neonatal dopamine system are not well characterized. The present study examined whether early manipulation of the dopamine system, a known mediator of adult prairie vole social behavior, during neonatal development would affect adult aggressive and attachment behaviors. Eight-day-old pups were given a single treatment with either 1mg/kg SKF38393 (D1 agonist), quinpirole (D2 agonist), SCH23390 (D1 antagonist), eticlopride (D2 antagonist), or saline vehicle. As adults, subjects received tests for intrasexual aggression and partner preference. Activation of D1-like receptors in pups impaired partner preference formation but had no effect on aggression. Other neonatal treatments had no effect on their behavior as adults. To determine if D1 activation in pups induced changes in dopamine receptor expression, we performed autoradiography on striatal tissue from a second cohort of saline and SKF38393 treated animals. Although sex differences were observed, we found no treatment differences in D1 or D2 receptor binding in any striatal sub-region. This study shows that exposure to a single early pharmacological alteration of dopamine receptor activity may have long-term effects on the social behavior of prairie voles.

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