冷漠
神经科学
帕金森病
多巴胺
纹状体
心理学
多巴胺能
疾病
多巴胺受体D3
多巴胺受体
医学
内科学
认知
作者
Mathieu Favier,Carole Carcenac,Marc Savasta,Sebastien Carnicella
出处
期刊:Current topics in behavioral neurosciences
日期:2022-01-01
卷期号:: 109-132
标识
DOI:10.1007/7854_2022_316
摘要
Parkinson's disease (PD), which is traditionally viewed as a motor disorder involving the degeneration of dopaminergic (DA) neurons, has recently been identified as a quintessential neuropsychiatric condition. Indeed, a plethora of non-motor symptoms may occur in PD, including apathy. Apathy can be defined as a lack of motivation or a deficit of goal-directed behaviors and results in a pathological decrease of self-initiated voluntary behavior. Apathy in PD appears to fluctuate with the DA state of the patients, suggesting a critical role of DA neurotransmission in the pathophysiology of this neuropsychiatric syndrome. Using a lesion-based approach, we developed a rodent model which exhibits specific alteration in the preparatory component of motivational processes, reminiscent to apathy in PD. We found a selective decrease of DA D3 receptors (D3R) expression in the dorsal striatum of lesioned rats. Next, we showed that inhibition of D3R neurotransmission in non-lesioned animals was sufficient to reproduce the motivational deficit observed in our model. Interestingly, we also found that pharmacologically targeting D3R efficiently reversed the motivational deficit induced by the lesion. Our findings, among other recent data, suggest a critical role of D3R in parkinsonian apathy and highlight this receptor as a promising target for treating motivational deficits.
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