Sackler Program for Epigenetics and Psychobiology at McGill University, Douglas Mental Health University Institute, McGill University, Montréal, Canada.
Endocrinology. 2010 May;151(5):2276-86. doi: 10.1210/en.2009-1271. Epub 2010 Mar 12.
Variations in maternal behavior among lactating rats associate with differences in estrogen-oxytocin interactions in the medial preoptic area (mPOA) and in dopamine levels in the nucleus accumbens (nAcc). Thus, stable, individual differences in pup licking/grooming (LG) are abolished by oxytocin receptor blockade or treatments that eliminate differences in the nAcc dopamine signal. We provide novel evidence for a direct effect of oxytocin at the level of the ventral tegmental area (VTA) in the regulation of nAcc dopamine levels. Mothers that exhibit consistently increased pup LG (i.e. high LG mothers) by comparison with low LG mothers show increased oxytocin expression in the mPOA and the paraventricular nucleus of the hypothalamus and increased projections of oxytocin-positive cells from both mPOA and paraventricular nucleus of the hypothalamus to the VTA. Direct infusion of oxytocin into the VTA increased the dopamine signal in the nAcc. Finally, high compared with low LG mothers show greater increases in dopamine signal in the nAcc during bouts of pup LG, and this difference is abolished with infusions of an oxytocin receptor antagonist directly into the VTA. These studies reveal a direct effect of oxytocin on dopamine release within the mesocorticolimbic dopamine system and are consistent with previous reports of oxytocin-dopamine interactions in the establishment and maintenance of social bonds.
哺乳期大鼠的母性行为变化与中脑导水管周围灰质(mPOA)中的雌激素-催产素相互作用和伏隔核(nAcc)中的多巴胺水平的差异有关。因此,催产素受体阻断或消除 nAcc 多巴胺信号差异的处理会消除稳定的个体幼鼠舔舐/梳理(LG)差异。我们提供了催产素在调节 nAcc 多巴胺水平方面在腹侧被盖区(VTA)水平直接作用的新证据。与低 LG 母亲相比,表现出持续增加幼鼠 LG(即高 LG 母亲)的母亲在 mPOA 和下丘脑室旁核中表现出更高的催产素表达,并增加了来自 mPOA 和下丘脑室旁核的催产素阳性细胞投射到 VTA。直接向 VTA 输注催产素会增加 nAcc 中的多巴胺信号。最后,与低 LG 母亲相比,高 LG 母亲在幼鼠 LG 期间表现出更大的 nAcc 多巴胺信号增加,并且这种差异在 VTA 直接输注催产素受体拮抗剂时被消除。这些研究揭示了催产素对中脑边缘多巴胺系统内多巴胺释放的直接影响,与先前关于催产素-多巴胺相互作用在社会联系的建立和维持中的报告一致。