Program in Neuroscience, University of Michigan, Ann Arbor, Michigan 48109, USA.
J Neurosci. 2012 May 16;32(20):6771-84. doi: 10.1523/JNEUROSCI.5779-11.2012.
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 κ-opioid receptors with the antagonist norbinaltorphimine (nor-BNI; 100 mg/kg), but not with the preferential μ-opioid receptor antagonist naloxone (1, 10, or 30 mg/kg), decreased selective aggression in males. We then provide the first comprehensive characterization of κ- and μ-opioid receptors in the prairie vole brain. Finally, we demonstrate that blockade of κ-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 κ-opioid receptors within the ventral pallidum or μ-opioid receptors with the specific μ-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, κ-opioid receptors within the NAc shell mediate aversive social motivation that is critical for pair bond maintenance.
草原田鼠是一种社会一夫一妻制的物种，繁殖对通常表现出强烈和选择性的配对纽带。配对纽带的建立与从一般依附到对新同种个体的攻击性拒绝的行为转变有关。这种“选择性攻击”表明了配偶保护的必要性，以维持最初的配对纽带。在实验室中，使用居住者-入侵者测试研究这种行为的神经生物学。尽管其他物种的社会行为是由内源性阿片系统介导的，但阿片调节对维持配对纽带的作用从未被研究过。在这里，我们使用居住者-入侵者测试来确定大脑动机回路中的内源性阿片系统是否介导草原田鼠的选择性攻击。我们首先表明，用拮抗剂诺比那醇（nor-BNI；100mg/kg）而非选择性 μ-阿片受体拮抗剂纳洛酮（1、10 或 30mg/kg）外周阻断 κ-阿片受体可降低雄性的选择性攻击。然后，我们提供了草原田鼠大脑中 κ-和 μ-阿片受体的首次全面特征描述。最后，我们证明了在伏隔核壳内阻断 κ-阿片受体（500ng nor-BNI）可消除雌雄两性的选择性攻击，但在伏隔核核内阻断这些受体可特异性增强雌性的这种行为。在伏隔核壳内阻断 κ-阿片受体或用特异性 μ-阿片受体拮抗剂 H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2（1ng CTAP）阻断 μ-阿片受体对两性均无影响。因此，伏隔核壳内的 κ-阿片受体介导对配偶保护至关重要的厌恶社交动机。
