Effects of prolonged selective serotonin reuptake inhibition on the development and expression of L-DOPA-induced dyskinesia in hemi-parkinsonian rats.
Effects of prolonged selective serotonin reuptake inhibition on the development and expression of L-DOPA-induced dyskinesia in hemi-parkinsonian rats.
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长时间选择性5-羟色胺再摄取抑制对Hemi-Parkinsonian大鼠L- dopa诱导的运动障碍的发育和表达的影响。
DOI：
10.1016/j.neuropharm.2013.09.017
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发表时间：
2014-02
影响因子：
4.7
通讯作者：
Bishop C
中科院分区：
文献类型：
--
作者：
Conti MM;Ostock CY;Lindenbach D;Goldenberg AA;Kampton E;Dell'isola R;Katzman AC;Bishop C
多巴胺（DA）替代左旋多巴治疗是帕金森病（PD）的标准治疗方法。不幸的是，慢性治疗经常导致异常不自主运动（AIMs）的发展，即左旋多巴诱导的运动障碍（LID）。越来越多的证据表明，5-羟色胺（5-HT）神经元的代偿可塑性有助于LID，最近的研究表明，急性5-羟色胺转运体（SERT）阻断提供抗运动障碍保护。然而，这些影响的持久性和机制都没有被研究过。因此，目前的努力是在左旋多巴启动和-naïve半帕金森大鼠中模拟SERT抑制的长期方案。大鼠接受选择性5-羟色胺再摄取抑制剂（SSRIs）西酞普兰（0、3或5 mg/kg）或帕罗西汀（0、0.5或1.25 mg/kg）与左旋多巴（6 mg/kg）每日联合治疗3周，期间监测AIMs和运动表现。为了研究潜在的作用机制，我们监测纹状体单胺的组织水平，并使用5-HT1A受体拮抗剂WAY100635 （0.5 mg/kg）。结果显示，长时间服用SSRIs可分别减弱l - dopa启动和-naïve受试者的AIMs表达和发育，但不影响运动表现。纹状体组织的神经化学分析表明，3周的SERT阻断使左旋多巴治疗大鼠的DA水平升高。在药理学上，抗运动障碍作用部分逆转了WAY100635，这表明参与了5-HT1A受体。总的来说，这些发现表明，延长SERT抑制部分通过5-HT1A受体提供持久的抗运动障碍作用，同时通过提高纹状体DA水平维持L-DOPA的抗帕金森病疗效。
Dopamine (DA) replacement therapy with L-DOPA is the standard treatment for Parkinson’s disease (PD). Unfortunately chronic treatment often leads to the development of abnormal involuntary movements (AIMs) referred to as L-DOPA-induced dyskinesia (LID). Accumulating evidence has shown that compensatory plasticity in serotonin (5-HT) neurons contributes to LID and recent work has indicated that acute 5-HT transporter (SERT) blockade provides anti-dyskinetic protection. However neither the persistence nor the mechanism(s) of these effects have been investigated. Therefore the current endeavor sought to mimic a prolonged regimen of SERT inhibition in L-DOPA-primed and –naïve hemi-parkinsonian rats. Rats received 3 weeks of daily co-treatment of the selective 5-HT reuptake inhibitors (SSRIs) citalopram (0, 3, or 5 mg/kg) or paroxetine (0, 0.5, or 1.25 mg/kg) with L-DOPA (6 mg/kg) during which AIMs and motor performance were monitored. In order to investigate potential mechanisms of action, tissue levels of striatal monoamines were monitored and the 5-HT1A receptor antagonist WAY100635 (0.5 mg/kg) was used. Results revealed that prolonged SSRIs attenuated AIMs expression and development in L-DOPA-primed and –naïve subjects, respectively, without interfering with motor performance. Neurochemical analysis of striatal tissue indicated that a 3 week SERT blockade increased DA levels in L-DOPA-treated rats. Pharmacologically, anti-dyskinetic effects were partially reversed with WAY100635 signifying involvement of the 5-HT1A receptor. Collectively, these findings demonstrate that prolonged SERT inhibition provides enduring anti-dyskinetic effects in part via 5-HT1A receptors while maintaining L-DOPA’s anti-parkinsonian efficacy by enhancing striatal DA levels.
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DOI：
10.1124/jpet.106.110429
发表时间：
2006-12-01
影响因子：
3.5
作者：
Iravani, Mahmoud M.;Tayarani-Binazir, Kayhan;Jenner, Peter
通讯作者：
Jenner, Peter
影响因子：
2.5
作者：
ARAI, R;KARASAWA, N;NAGATSU, I
通讯作者：
NAGATSU, I
影响因子：
11.2
作者：
HALLIDAY, GM;LI, YW;GEFFEN, LB
通讯作者：
GEFFEN, LB
影响因子：
9.9
作者：
Bibbiani, F;Oh, JD;Chase, TN
通讯作者：
Chase, TN
影响因子：
3.3
作者：
Chang, JW;Wachtel, SR;Kang, UJ
通讯作者：
Kang, UJ