伏隔核
纹状体
神经科学
多巴胺受体D2
奖励制度
多巴胺
突触后电位
心理学
腹侧纹状体
上瘾
受体
医学
内科学
作者
Pierre Trifilieff,Bo Feng,Eneko Urizar,Vanessa Winiger,Ryan D. Ward,Kathleen Taylor,Diana Martínez,Holly Moore,Peter D. Balsam,Eleanor H. Simpson,Jonathan A. Javitch
摘要
A decrease in dopamine D2 receptor (D2R) binding in the striatum is one of the most common findings in disorders that involve a dysregulation of motivation, including obesity, addiction and attention deficit hyperactivity disorder. As disruption of D2R signaling in the ventral striatum—including the nucleus accumbens (NAc)—impairs motivation, we sought to determine whether potentiating postsynaptic D2R-dependent signaling in the NAc would improve motivation. In this study, we used a viral vector strategy to overexpress postsynaptic D2Rs in either the NAc or the dorsal striatum. We investigated the effects of D2R overexpression on instrumental learning, willingness to work, use of reward value representations and modulation of motivation by reward associated cues. Overexpression of postsynaptic D2R in the NAc selectively increased motivation without altering consummatory behavior, the representation of the value of the reinforcer, or the capacity to use reward associated cues in flexible ways. In contrast, D2R overexpression in the dorsal striatum did not alter performance on any of the tasks. Thus, consistent with numerous studies showing that reduced D2R signaling impairs motivated behavior, our data show that postsynaptic D2R overexpression in the NAc specifically increases an animal’s willingness to expend effort to obtain a goal. Taken together, these results provide insight into the potential impact of future therapeutic strategies that enhance D2R signaling in the NAc.
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