The role of dopamine pharmacotherapy and addiction-like behaviors in Parkinson's disease
The role of dopamine pharmacotherapy and addiction-like behaviors in Parkinson's disease
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DOI：
10.1016/j.pnpbp.2020.109942
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发表时间：
2020-08-30
影响因子：
5.6
通讯作者：
Persons, Amanda L.
中科院分区：
文献类型：
--
作者：
Napier, T. Celeste;Kirby, Alana;Persons, Amanda L.
成瘾涉及一系列行为，包括冲动性和强迫性的特征，这里称为冲动性-强迫性谱系障碍（icsd）。icsd的病因可能涉及神经生物学、心理和社会风险因素之间复杂的相互作用。神经生物学危险因素包括控制icsd的神经解剖学回路的状态。这些回路可以被疾病改变，也可以被外源性影响如中枢作用的药理学改变。这种情况的“典型代表”是帕金森病（PD），通过药物治疗进行医学管理。PD是一种进行性神经退行性疾病，主要涉及黑质纹状体投射内多巴胺能神经元的逐渐丧失。替代疗法包括直接激活突触后多巴胺受体的多巴胺受体激动剂（绕过突触前终末功能的要求）。一些临床上有用的多巴胺激动剂，如普拉克索和罗匹尼罗，对D2/D3受体亚型表现出高亲和力。这些激动剂可以很好地缓解PD运动症状，但一些患者表现出使人衰弱的ICSD。从用于治疗PD运动症状的药物中梳理出PD相关病理的神经精神贡献是具有挑战性的。在这篇综述中，我们假设现代临床和临床前研究都集中在多巴胺替代疗法可以介导PD和其他神经系统疾病的成瘾。我们提供了与这一观点一致的五类证据：(i) D2/D3受体激动剂治疗比单独PD治疗的ICSD患病率更高。（二）多巴胺替代疗法产生成瘾样行为的能力与所提供治疗的疾病无关。（iii）在有或没有pd样病理的实验室大鼠中重现icsd样行为。（iv）行为病理学与药物暴露相关。(v) ICSD的特征与激动剂药理学和成瘾的神经解剖学基础一致。考虑PD中icsd的基础不仅有助于神经系统疾病的治疗决策，而且还有助于一般icsd的通报。
Addictions involve a spectrum of behaviors that encompass features of impulsivity and compulsivity, herein referred to as impulsive-compulsive spectrum disorders (ICSDs). The etiology of ICSDs likely involves a complex interplay among neurobiological, psychological and social risk factors. Neurobiological risk factors include the status of the neuroanatomical circuits that govern ICSDs. These circuits can be altered by disease, as well as exogenous influences such as centrally-acting pharmacologics. The 'poster child' for this scenario is Parkinson's disease (PD) medically managed by pharmacological treatments. PD is a progressive neurodegenerative disease that involves a gradual loss of dopaminergic neurons largely within nigrostriatal projections. Replacement therapy includes dopamine receptor agonists that directly activate postsynaptic dopamine receptors (bypassing the requirement for functioning presynaptic terminals). Some clinically useful dopamine agonists, e.g., pramipexole and ropinirole, exhibit high affinity for the D2/D3 receptor subtypes. These agonists provide excellent relief from PD motor symptoms, but some patients exhibit debilitating ICSD. Teasing out the neuropsychiatric contribution of PD-associated pathology from the drugs used to treat PD motor symptoms is challenging. In this review, we posit that modern clinical and preclinical research converge on the conclusion that dopamine replacement therapy can mediate addictions in PD and other neurological disorders. We provide five categories of evidences that align with this position: (i) ICSD prevalence is greater with D2/D3 receptor agonist therapy vs PD alone. (ii) Capacity of dopamine replacement therapy to produce addiction-like behaviors is independent of disease for which the therapy is being provided. (iii) ICSD-like behaviors are recapitulated in laboratory rats with and without PD-like pathology. (iv) Behavioral pathology co-varies with drug exposure. (v) ICSD Features of ICSDs are consistent with agonist pharmacology and neuroanatomical substrates of addictions. Considering the underpinnings of ICSDs in PD should not only help therapeutic decision-making in neurological disorders, but also apprise ICSDs in general.