Breese G R, Criswell H E, Duncan G E, Mueller R A
Psychopharmacol Bull. 1989;25(3):353-7.
Based on the report that patients with Lesch-Nyhan Syndrome (LNS) have a central deficiency of dopamine similar in magnitude to that seen in Parkinsonism, the age at which dopaminergic neurons are disrupted was proposed to explain the differing symptoms observed in these two disorders. To investigate this hypothesis, brain dopaminergic neurons were lesioned in neonatal and adult rats with 6-hydroxy-dopamine (6-OHDA). Results demonstrated that neonatally lesioned rats had learning deficits and elevated levels of serotonin in the striatum--characteristics observed in LNS. Administration of L-dopa produced self-injurious behavior (SIB) in neonatally lesioned but not adult lesioned rats. Subsequent studies revealed that the SIB induced by L-dopa was dependent upon activation of D1 receptors. The elevated susceptibility of neonatally lesioned rats for SIB was demonstrated further by the enhanced occurrence of SIB when muscimol was administered into the substantia nigra reticulata (SNR). Other studies demonstrated that adenosine agonists could antagonize SIB, suggesting that the reduced adenosine observed in LNS may contribute to this symptom. The basic work being performed should be relevant to LNS and to other developmental disorders exhibiting SIB.
基于报告称莱施-奈恩综合征（LNS）患者存在与帕金森病中程度相似的多巴胺中枢缺乏，有人提出多巴胺能神经元被破坏的年龄可解释这两种疾病中观察到的不同症状。为了研究这一假设，用6-羟基多巴胺（6-OHDA）损毁新生大鼠和成年大鼠的脑多巴胺能神经元。结果表明，新生期损毁的大鼠有学习缺陷且纹状体中血清素水平升高——这是在LNS中观察到的特征。给予左旋多巴在新生期损毁而非成年期损毁的大鼠中产生了自伤行为（SIB）。随后的研究表明，左旋多巴诱导的SIB依赖于D1受体的激活。当向黑质网状部（SNR）注射蝇蕈醇时SIB发生率增加，这进一步证明了新生期损毁的大鼠对SIB的易感性增强。其他研究表明腺苷激动剂可拮抗SIB，提示在LNS中观察到的腺苷减少可能导致了这种症状。正在进行的基础研究应该与LNS以及其他表现出自伤行为的发育障碍相关。
