Genetic Approaches to the Neurobiology of Electroconvulsive Therapy
Genetic Approaches to the Neurobiology of Electroconvulsive Therapy
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DOI：
10.1097/00124509-199809000-00006
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发表时间：
1998-09
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影响因子：
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通讯作者：
L. Fochtmann
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文献类型：
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作者：
L. Fochtmann
尽管电休克疗法可以有效治疗严重的精神疾病，但其神经生物学机制尚不完全清楚。同样不清楚的是患者癫痫发作阈值和持续时间变异的基础。我们使用多种大鼠和小鼠品系来测试电休克（ECS）引起的癫痫发作特性的遗传变异。我们专门测量了癫痫发作持续时间、对咖啡因促惊厥作用的敏感性以及对发作后诱导进一步癫痫发作的相对难治性，所有这些都显示出显着的菌株间变异性。此外，强直阵挛发作持续时间与立即死亡率相关，表明不同品系细胞兴奋性的潜在水平存在差异。通过使用定量放射自显影将这些发现与神经生物学机制联系起来，我们发现海马 A1 受体结合、皮质和纹状体 N-甲基-D-天冬氨酸 (NMDA) 受体结合以及咖啡因对癫痫持续时间的改变之间存在显着相关性。这些研究表明，遗传因素调节电诱发癫痫发作的神经生物学决定因素。此外，他们认为遗传因素可能导致临床观察到的癫痫阈值的变异。最后，这些数据为未来的分子遗传学方法提供了基础，将 ECS 引起的癫痫发作特性的变化与相关的发射系统联系起来。
Although electroconvulsive therapy effectively treats severe psychiatric disorders, its neurobiologic mechanisms are not fully understood. Also unclear is the basis for variability in seizure threshold and duration among patients. We used multiple strains of rats and mice to test for genetic variation in the properties of seizures induced by electroconvulsive shock (ECS). We specifically measured seizure duration, sensitivity to proconvulsant actions of caffeine, and relative refractoriness to postictal induction of further seizures, all of which showed significant interstrain variability. In addition, tonic-clonic seizure durations correlated with rates of immediate mortality, suggesting variations in underlying levels of cellular excitability across strains. By using quantitative autoradiography to relate these findings to neurobiologic mechanisms, we found significant correlations between hippocampal A1-receptor binding, cortical and striatal N-methyl-D-aspartate (NMDA)-receptor binding, and the modification of seizure duration by caffeine. These studies suggest that heritable factors modulate the neurobiologic determinants of electrically induced seizures. Furthermore, they suggest that genetic factors may contribute to clinically observed variability in seizure thresholds. Finally, the data provide a basis for future molecular genetic approaches to link ECS-induced changes in seizure properties to relevant transmitter systems.