Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA.
Psychopharmacology (Berl). 2012 Nov;224(2):303-12. doi: 10.1007/s00213-012-2753-6. Epub 2012 Jun 6.
Agonists at the mu opioid receptor (MOR) are widely recognized for their effects on reward and pain. Although prior studies have attributed some of these effects to MORs on GABA neurons in the ventral tegmental area (VTA), recent studies have identified a region of particularly strong MOR immunostaining residing caudal to the VTA, in a region denoted the rostromedial tegmental nucleus (RMTg).
Hence, we examined whether rats would self-administer small doses (50-250 pmol) of the selective MOR agonist endomorphin-1 (EM1) into the RMTg and adjacent sites. EM1 was chosen due to its short half-life, thus limiting drug spread, and due to its presence endogenously in brain neurons, including some afferents to the RMTg.
The highest rates of EM1 self-administration occurred within 0.5 mm of the RMTg center, in a region roughly 0.8-1.6 mm caudal to the majority of VTA DA neurons. In contrast, self-administration rates were much lower in the adjacent VTA, interpeduncular nucleus, central linear nucleus, or median raphe nucleus. Furthermore, EM1 infusions into the RMTg, but not surrounding regions, produced conditioned place preference, while EM1 infusions into the RMTg but not anterior VTA markedly reduced formalin-induced pain behaviors. EM1 effects were mimicked by infusions of the GABA agonist muscimol into the same region, consistent with EM1 having inhibitory actions on its target neurons.
These results implicate a novel brain region in modulating MOR influences on both appetitive and aversive behavior.
μ 阿片受体（MOR）激动剂因其对奖赏和疼痛的影响而被广泛认可。尽管先前的研究将这些效应中的一些归因于腹侧被盖区（VTA）中的 GABA 神经元上的 MOR，但最近的研究已经确定了一个位于 VTA 尾部的特别强烈的 MOR 免疫染色区域，该区域被称为穹隆内侧被盖核（RMTg）。
因此，我们检查了大鼠是否会将小剂量（50-250 pmol）的选择性 MOR 激动剂内吗啡肽-1（EM1）自行注射到 RMTg 及其相邻部位。选择 EM1 是因为它的半衰期短，从而限制了药物的扩散，并且因为它存在于脑神经元中，包括一些投射到 RMTg 的神经元。
EM1 自我给药的最高速率发生在 RMTg 中心 0.5mm 内，位于 VTA DA 神经元的大部分尾部约 0.8-1.6mm 的区域内。相比之下，相邻的 VTA、脚间核、中央线性核或中缝核中的自我给药率要低得多。此外，EM1 注入 RMTg 而不是周围区域会产生条件性位置偏好，而 EM1 注入 RMTg 而不是前 VTA 会显著减少福尔马林引起的疼痛行为。将 GABA 激动剂 muscimol 注入同一区域可模拟 EM1 的作用，这与 EM1 对其靶神经元具有抑制作用一致。
这些结果表明，一个新的脑区在调节 MOR 对食欲和厌恶行为的影响方面具有重要作用。
