Mapping of reinforcing and analgesic effects of the mu opioid agonist endomorphin-1 in the ventral midbrain of the rat.
Mapping of reinforcing and analgesic effects of the mu opioid agonist endomorphin-1 in the ventral midbrain of the rat.
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DOI：
10.1007/s00213-012-2753-6
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发表时间：
2012-11
影响因子：
3.4
通讯作者：
Ikemoto, Satoshi
中科院分区：
文献类型：
--
作者：
Jhou, Thomas C.;Xu, Sheng-Ping;Lee, Mary R.;Gallen, Courtney L.;Ikemoto, Satoshi
μ阿片受体（莫尔）激动剂因其对奖赏和疼痛的作用而被广泛认可。虽然先前的研究已将这些影响中的一些归因于MOR对腹侧被盖区（VTA）中的GABA神经元的影响，但最近的研究已确定了位于腹侧被盖区尾侧的特别强的莫尔免疫染色区域，该区域被称为头内侧被盖核（RMTg）。因此，我们检查了大鼠是否将小剂量（50-250 pmol）的选择性莫尔激动剂内吗啡肽-1（EM 1）自我施用到RMTg和邻近部位。选择EM 1是因为其半衰期短，从而限制了药物扩散，并且由于其内源性存在于脑神经元中，包括RMTg的一些传入。EM 1自我给药的最高速率发生在RMTg中心的0.5 mm内，在大多数VTA DA神经元尾部大约0.8-1.6 mm的区域。相比之下，在邻近的腹侧被盖区、脚间核、中央线状核或中缝核中，自我给药率要低得多。此外，EM 1注入到RMTg，而不是周围地区，产生条件性的位置偏好，而EM 1注入到RMTg，而不是前腹侧被盖区显着减少福尔马林引起的疼痛行为。通过将GABA激动剂蝇蕈醇输注到相同区域中来模拟EM 1的作用，这与EM 1对其靶神经元具有抑制作用一致。这些结果暗示了一个新的大脑区域在调节莫尔对食欲和厌恶行为的影响。
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.
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影响因子：
2.5
作者：
Balcita-Pedicino, Judith Joyce;Omelchenko, Natalia;Bell, Roland;Sesack, Susan R.
通讯作者：
Sesack, Susan R.
影响因子：
3
作者：
Ikemoto, S;Sharpe, LG
通讯作者：
Sharpe, LG
影响因子：
3.6
作者：
Houdi, AA;Kottayil, S;Butterfield, DA
通讯作者：
Butterfield, DA
影响因子：
16.2
作者：
Jhou, Thomas C.;Fields, Howard L.;Baxter, Mark G.;Saper, Clifford B.;Holland, Peter C.
通讯作者：
Holland, Peter C.
影响因子：
6.1
作者：
BOZARTH, MA;WISE, RA
通讯作者：
WISE, RA