Activation of μ-Opioid Receptors in the Dorsal Striatum is Necessary for Adult Social Attachment in Monogamous Prairie Voles
Activation of μ-Opioid Receptors in the Dorsal Striatum is Necessary for Adult Social Attachment in Monogamous Prairie Voles
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DOI：
10.1038/npp.2011.117
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发表时间：
2011-10-01
影响因子：
7.6
通讯作者：
Young, Larry J.
中科院分区：
文献类型：
--
作者：
Burkett, James P.;Spiegel, Lauren L.;Young, Larry J.
尽管有大量证据表明阿片类药物通过中介社会奖励和动机参与依恋，但阿片类药物在成人社会依恋形成中的作用尚未被探索。我们以社会一夫一妻制草原田鼠（Microtus ochrogaster）为研究对象，通过考察雌性草原田鼠的伴侣偏好形成，探讨内源性阿片类物质在社会联系中的作用。我们假设纹状体中的m-阿片受体（MORs）在伴侣偏好形成中起关键作用。因此，我们预测外周给药阿片受体拮抗剂会抑制伴侣偏好的形成，更具体地说，纹状体内的m-阿片选择性受体阻断会抑制伴侣偏好的形成。为了验证我们的假设，我们首先在女性与男性同居18小时期间外周给予非选择性阿片类拮抗剂纳曲酮，然后用伴侣偏好测试（PPT）对女性进行测试。女性在PPT中表现出剂量计划依赖性的伴侣偏好减少，而连续剂量组的女性表现出陌生人偏好。接下来，我们在与雄性小鼠同居24小时之前，将MOR选择性拮抗剂d - phe - cys - tyrr - d - trp - arg - thr - pen - thr - nh2 （CTAP）显微注射到伏隔核壳（NAS）或尾壳核（CP），随后用PPT测试雌性小鼠。雌性接受CTAP进入CP，而不是NAS，对PPT没有偏好，表明伴侣偏好形成受到抑制。我们首次发现MORs通过作用于CP调节雌性草原田鼠的伴侣偏好形成。神经精神药理学（2011）36,2200-2210；doi: 10.1038 / npp.2011.117;2011年7月6日在线发布
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. Neuropsychopharmacology (2011) 36, 2200-2210; doi: 10.1038/npp.2011.117; published online 6 July 2011