Department of Psychology, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL, 60626, USA.
Department of Psychology, Loyola University Chicago, 1032 West Sheridan Road, Chicago, IL, 60626, USA.
Behav Brain Res. 2020 Feb 3;379:112340. doi: 10.1016/j.bbr.2019.112340. Epub 2019 Nov 4.
The rostromedial tegmental nucleus (RMTg) receives inputs from the laterodorsal tegmental and pedunculopontine tegmental nuclei, the two principle brainstem cholinergic nuclei. We tested the effects of RMTg M3 and M4 muscarinic cholinergic receptor antagonism in a conditioned place preference (CPP) paradigm in mice. RMTg infusions of the M3 muscarinic cholinergic receptor antagonist 1,1-Dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) do not result in the acquisition of CPP but increase locomotor activation. By contrast, RMTg infusions of the M4 muscarinic cholinergic receptor antagonist Tropicamide result in the acquisition of CPP but do not increase locomotor activation. The rewarding effects of RMTg Tropicamide infusions are dopamine-dependent as systemic pre-treatment with the broad-spectrum dopamine receptor antagonist flupenthixol prevents the acquisition of CPP induced by RMTg Tropicamide infusions. Under conditions of systemic dopamine receptor blockade, RMTg Tropicamide infusions significantly increase locomotor activation. These data provide further support for an important role of endogenous cholinergic input to the RMTg in reward function and suggest that the contributions of RMTg cholinergic input to rewarding and locomotor-activating effects involve differential contributions of RMTg M4 and M3 muscarinic receptors, respectively.
中脑被盖腹侧区（RMTg）接收来自外侧背侧被盖核和脚桥核被盖的输入，这两个是主要的脑干胆碱能核。我们在小鼠条件性位置偏好（CPP）范式中测试了 RMTg M3 和 M4 毒蕈碱型乙酰胆碱受体拮抗作用的影响。RMTg 输注 M3 毒蕈碱型乙酰胆碱受体拮抗剂 1,1-二甲基-4-二苯乙酰氧基哌啶碘化物（4-DAMP）不会导致 CPP 的获得，但会增加运动激活。相比之下，RMTg 输注 M4 毒蕈碱型乙酰胆碱受体拮抗剂托品酰胺会导致 CPP 的获得，但不会增加运动激活。RMTg 托品酰胺输注的奖赏效应是多巴胺依赖性的，因为全身给予广谱多巴胺受体拮抗剂氟哌噻吨可以防止 RMTg 托品酰胺输注引起的 CPP 的获得。在系统多巴胺受体阻断的情况下，RMTg 托品酰胺输注会显著增加运动激活。这些数据进一步支持内源性胆碱能输入到 RMTg 在奖赏功能中的重要作用，并表明 RMTg 胆碱能输入对奖赏和运动激活效应的贡献分别涉及 RMTg M4 和 M3 毒蕈碱型受体的不同贡献。
