A threshold model for opposing actions of acetylcholine on reward behavior: Molecular mechanisms and implications for treatment of substance abuse disorders.
A threshold model for opposing actions of acetylcholine on reward behavior: Molecular mechanisms and implications for treatment of substance abuse disorders.
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DOI：
10.1016/j.bbr.2016.06.022
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发表时间：
2016-10-01
影响因子：
2.7
通讯作者：
Grasing K
中科院分区：
文献类型：
--
作者：
Grasing K
胆碱能系统在学习和成瘾中起着重要作用。改变胆碱能张力的药物可以对自然和药物增强的行为产生明显的影响。重要的是，增强乙酰胆碱（ACh）在丘脑腹侧被盖区（VTA）多巴胺系统中的作用可以增强或减弱这些行为。阈值模型，可以解释这些看似矛盾的结果。相对较低水平的乙酰胆碱上升到较低的阈值以上，促进药物或天然维生素支持的行为。胆碱能紧张度的进一步增加超过第二阈值上限，则会对抗相同的行为。因此，胆碱酯酶抑制剂，或烟碱或毒蕈碱受体激动剂，都有可能对奖励行为产生双相效应。用烟碱或毒蕈碱拮抗剂预处理可以通过维持胆碱能张力低于其下限来阻断药物或食物强化的行为。潜在的阈值介质包括烟碱受体的脱敏和ACh对中型棘神经元放电的双相效应。高亲和力和低亲和力的烟碱受体似乎分别在奖赏增强和抑制中发挥更大的作用。胆碱能抑制的自然和药物奖励可能作为介质先前描述的对手的过程。未来的研究应该在更广泛的剂量范围内评估胆碱能药物，并包括各种强化行为。
The cholinergic system plays important roles in both learning and addiction. Medications that modify cholinergic tone can have pronounced effects on behaviors reinforced by natural and drug reinforcers. Importantly, enhancing the action of acetylcholine (ACh) in the nucleus accumbens and ventral tegmental area (VTA) dopamine system can either augment or diminish these behaviors. A threshold model is presented that can explain these seemingly contradictory results. Relatively low levels of ACh rise above a lower threshold, facilitating behaviors supported by drugs or natural reinforcers. Further increases in cholinergic tone that rise above a second upper threshold oppose the same behaviors. Accordingly, cholinesterase inhibitors, or agonists for nicotinic or muscarinic receptors, each have the potential to produce biphasic effects on reward behaviors. Pretreatment with either nicotinic or muscarinic antagonists can block drug- or food- reinforced behavior by maintaining cholinergic tone below its lower threshold. Potential threshold mediators include desensitization of nicotinic receptors and biphasic effects of ACh on the firing of medium spiny neurons. Nicotinic receptors with high- and low-affinity appear to play greater roles in reward enhancement and inhibition, respectively. Cholinergic inhibition of natural and drug rewards may serve as mediators of previously described opponent processes. Future studies should evaluate cholinergic agents across a broader range of doses, and include a variety of reinforced behaviors.