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At-risk for pathological gambling: imaging neural reward processing under chronic dopamine agonists.
病态赌博的风险: 慢性多巴胺激动剂下的成像神经奖励处理。

摘要

Treatment with dopamine receptor agonists has been associated with impulse control disorders and pathological gambling (PG) secondary to medication in previously unaffected patients with Parkinson's disease or restless legs syndrome (RLS). In a within-subjects design, we investigated the underlying neurobiology in RLS patients using functional magnetic resonance imaging. We scanned 12 female RLS patients without a history of PG. All patients were scanned twice: once whilst taking their regular medication with low dose dopamine receptor agonists and once after a washout phase interval. They performed an established gambling game task involving expectation and receipt or omission of monetary rewards at different levels of probabilities. Upon expectation of rewards, reliable ventral striatal activation was detected only when patients were on, but not when patients were off medication. Upon receipt or omission of rewards, the observed ventral striatal signal under medication differed markedly from its predicted pattern which by contrast was apparent when patients were off medication. Orbitofrontal activation was not affected by medication. Chronic dopamine receptor agonist medication changed the neural signalling of reward expectation predisposing the dopaminergic reward system to mediate an increased appetitive drive. Even without manifest PG, chronic medication with dopamine receptor agonists led to markedly changed neural processing of negative consequences probably mediating dysfunctional learning of contingencies. Intact orbitofrontal functioning, potentially moderating impulse control, may explain why none of the patients actually developed PG. Our results support the notion of a general medication effect in patients under dopamine receptor agonists in terms of a sensitization towards impulse control disorders.

译文

Treatment with dopamine receptor agonists has been associated with impulse control disorders and pathological gambling (PG) secondary to medication in previously unaffected patients with Parkinson's disease or restless legs syndrome (RLS). In a within-subjects design, we investigated the underlying neurobiology in RLS patients using functional magnetic resonance imaging. We scanned 12 female RLS patients without a history of PG. All patients were scanned twice: once whilst taking their regular medication with low dose dopamine receptor agonists and once after a washout phase interval. They performed an established gambling game task involving expectation and receipt or omission of monetary rewards at different levels of probabilities. Upon expectation of rewards, reliable ventral striatal activation was detected only when patients were on, but not when patients were off medication. Upon receipt or omission of rewards, the observed ventral striatal signal under medication differed markedly from its predicted pattern which by contrast was apparent when patients were off medication. Orbitofrontal activation was not affected by medication. Chronic dopamine receptor agonist medication changed the neural signalling of reward expectation predisposing the dopaminergic reward system to mediate an increased appetitive drive. Even without manifest PG, chronic medication with dopamine receptor agonists led to markedly changed neural processing of negative consequences probably mediating dysfunctional learning of contingencies. Intact orbitofrontal functioning, potentially moderating impulse control, may explain why none of the patients actually developed PG. Our results support the notion of a general medication effect in patients under dopamine receptor agonists in terms of a sensitization towards impulse control disorders.

Dopamine Agonists

神经 临床用药 治疗药物
概述  :  

多巴胺受体激动剂作为左旋多巴疗法的辅助用药,能够减少或取代左旋多巴的使用,减轻副作用。作用机制多巴胺受体激动剂是一类功能和结构上与多巴胺相似并可以直接作用于多巴胺受体的药物。目前上市的多巴胺受体激动剂均作用于D2受体而起作用,不同的多巴胺受体激动剂还分别作用于D1受体或D3受体,使直接通路和间接通路恢复正常或接近正常的状态从而起到治疗作用。如溴隐亭直接刺激D2受体,对D1受体有微弱的抑制作用;吡贝地尔(泰舒达)激活D2和D3受体;而甲磺酸培高利特(协良行)则同时作用于D1和D2受体。副作用与

dopamine  英 ['dəʊpəmiːn]   ['dopəmin] 

         n. [生化] 多巴胺(一种治脑神经病的药物)

        dopamine transporter 多巴胺转运蛋白多巴胺转运体多巴胺转运体基因脑多巴胺转运蛋白

    dopamine DA 多巴胺

    dopamine hypothesis 多巴胺假说

       We believed that this change would enhance dopamine activity in the brain.  我们认为这种改变可以增强脑内的多巴胺的功能。

 

agonist  英 ['ægənɪst]   ['ægənɪst] 

      n. 收缩筋;兴奋剂

      With study development of CCK receptor antagonist and agonist, people have deepunderstanding about CCK's physiological function.  CCK受体激动剂与拮抗剂的研究深入,促进了人们对CCK生理功能的深入认识。

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