Division of Behavioral Neuroscience and Psychiatric Disorders, Department of Psychiatry and Behavioral Sciences, Center for Translational Social Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Neuropsychopharmacology. 2011 Oct;36(11):2200-10. doi: 10.1038/npp.2011.117. Epub 2011 Jul 6.
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 μ-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 μ-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.
尽管有大量证据表明阿片类药物通过介导社会奖励和动机参与依恋,但阿片类药物在成年社交依恋形成中的作用尚未得到探索。我们使用社会一夫一妻制的草原田鼠(Microtus ochrogaster)来探索内源性阿片类物质在社交结合中的作用,方法是检查雌性草原田鼠的伴侣偏好形成。我们假设纹状体中的μ-阿片受体(MOR)在伴侣偏好形成中具有关键作用。因此,我们预测外周给予阿片受体拮抗剂会抑制伴侣偏好的形成,更具体地说,纹状体中的μ-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,我们首先在雌性与雄性 18 小时同居期间外周给予非选择性阿片拮抗剂纳曲酮,并在随后的伴侣偏好测试(PPT)中测试雌性。雌性在 PPT 中表现出剂量依赖性的伴侣偏好降低,持续剂量组的雌性表现出对陌生者的偏好。接下来,我们在与雄性 24 小时同居之前,立即将 MOR 选择性拮抗剂 D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2(CTAP)微注射到伏隔核壳(NAS)或尾壳核(CP)中,并在 PPT 中测试雌性。接受 CP 中的 CTAP 但不接受 NAS 中的 CTAP 的雌性在 PPT 中没有表现出偏好,表明其抑制了伴侣偏好的形成。我们首次表明,MOR 通过在 CP 中起作用来调节雌性草原田鼠的伴侣偏好形成。