Intrastriatal serotonin 5-HT2 receptors mediate dopamine D1-induced hyperlocomotion in 6-hydroxydopamine-lesioned rats.
Intrastriatal serotonin 5-HT2 receptors mediate dopamine D1-induced hyperlocomotion in 6-hydroxydopamine-lesioned rats.
复制标题
纹状体内血清素 5-HT2 受体介导 6-羟基多巴胺损伤大鼠中多巴胺 D1 诱导的过度运动。
DOI：
10.1002/syn.10253
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Walker,PaulD
中科院分区：
文献类型：
--
作者：
Bishop,Christopher;Kamdar,DevP;Walker,PaulD
Striatal dopamine (DA) and serotonin (5‐HT) functions are altered following DA denervation. Previous research indicates that intrastriatal coadministration of D1 and 5‐HT2 receptor agonists synergistically increase locomotor behavior in DA‐depleted rats. In the present study, we examined whether striatal 5‐HT2 mechanisms also account for supersensitive D1‐mediated locomotor behavior following DA denervation. Adult male Sprague‐Dawley rats were subjected to bilateral striatal cannulation and then received either intracerebroventricular (i.c.v.) or intrastriatal 6‐hydroxydopamine (6‐OHDA; 200 μg or 20 μg/side, respectively). After at least 3 weeks, i.c.v.‐lesioned rats received intrastriatal infusions of the 5‐HT2 receptor antagonist ritanserin (2.0 μg/side) or its vehicle (DMSO) followed by systemic SKF 82958, a D1 agonist (1.0 mg/kg, i.p.) and locomotor activity was monitored. In another experiment, intrastriatal sham and 6‐OHDA‐lesioned rats received bilateral intrastriatal infusions of ritanserin (2.0 μg/side) or its vehicle (DMSO) followed by intrastriatal infusions of SKF 82958 (5.0 μg/side) or vehicle (0.9% saline). Rats with DA loss demonstrated supersensitive locomotor responses to both systemic and intrastriatal SKF 82958. Ritanserin pretreatment blunted systemic SKF 82958‐induced hyperlocomotion and returned intrastriatal D1‐mediated hyperactivity to sham lesion levels. The results of this study suggest that striatal 5‐HT2 receptors contribute to D1‐mediated hyperkinesias resulting from DA loss and suggest a pharmacological target for the alleviation of dyskinesia that can develop with continued DA replacement therapy. Synapse 50:164–170, 2003. © 2003 Wiley‐Liss, Inc.
