Muscarinic cholinergic receptor antagonists in the VTA and RMTg have opposite effects on morphine-induced locomotion in mice.
Muscarinic cholinergic receptor antagonists in the VTA and RMTg have opposite effects on morphine-induced locomotion in mice.
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DOI：
10.1016/j.bbr.2017.01.039
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发表时间：
2017-04-14
影响因子：
2.7
通讯作者：
Ludwig J
中科院分区：
文献类型：
--
作者：
Steidl S;Dhillon ES;Sharma N;Ludwig J
腹侧被盖区（VTA）和嘴内侧被盖核（RMTg）各自对阿片奖励做出贡献，并且各自接收来自背侧被盖核和脚桥被盖核（两个主要脑干胆碱能细胞群）的输入。我们比较了VTA或RMTg毒蕈碱胆碱能受体对吗啡注入相同部位引起的运动的贡献。腹侧被盖区共同输注阿托品完全阻断腹侧被盖区吗啡诱导的运动提供了额外的支持的重要作用，腹侧被盖区毒蕈碱胆碱能受体的阿片类药物的刺激作用。相比之下，阿托品的RMTg共输注增加了RMTg吗啡诱导的运动。此外，RMTg共输注M3选择性拮抗剂4-DAMP，但不是M4选择性拮抗剂托吡卡胺，强烈增加RMTg吗啡诱导的运动。RMTg输注4-DAMP，而不是托吡卡胺，本身强烈增加无药物运动。因此，RMTg中的毒蕈碱胆碱能受体也有助于吗啡的兴奋作用，但与VTA中的受体相反。我们认为，净效应的内源性胆碱能输入的RMTg无药物和RMTg吗啡诱导的运动是抑制性的。
The ventral tegmental area (VTA) and the rostromedial tegmental nucleus (RMTg) each contribute to opiate reward and each receive inputs from the laterodorsal tegmental and pedunculopontine tegmental nuclei, the two principle brainstem cholinergic cell groups. We compared the contributions of VTA or RMTg muscarinic cholinergic receptors to locomotion induced by morphine infusions into the same sites. VTA co-infusion of atropine completely blocked VTA morphine-induced locomotion providing additional support for the important role of VTA muscarinic cholinergic receptors in the stimulant effects of opiates. By contrast, RMTg co-infusion of atropine increased RMTg morphine-induced locomotion. Furthermore, RMTg co-infusion of the M3-selective antagonist 4-DAMP, but not the M4-selective antagonist Tropicamide, strongly increased RMTg morphine-induced locomotion. RMTg infusions of 4-DAMP, but not of Tropicamide, by themselves strongly increased drug-free locomotion. Muscarinic cholinergic receptors in the RMTg thus also contribute to the stimulant effects of morphine, but in a way opposite to those in VTA. We suggest that the net effect of endogenous cholinergic input to the RMTg on drug-free and on RMTg morphine-induced locomotion is inhibitory.