ヒトiPS細胞由来ドーパミンニューロンの電気活動を用いた依存症評価法の検証

抄録

Dependence is known to be caused by various compounds such as frequently used medicines, luxury goods, and illegal drugs, and there is a need to establish an evaluation system for side effects to prevent the formation of dependence. However, a method for evaluating addiction has not yet been established. In this study, we constructed an evaluation system to detect addiction-positive compounds by measuring the electrical activity of iPS cell-derived dopamine neurons using microelectrode arrays (MEAs). The iCell dopamine neurons and iCell astrocytes were co-cultured on AXION MEAs. After 35 days of culture, we performed a cumulative administration test of 20 addiction-related compounds and measured the changes in electrical activity. Next, we conducted a chronic administration test of 10 addiction-related compounds and compared the results with those of the acute administration test using principal component analysis. In the cumulative administration experiment using dopamine neurons, it was possible to detect different responses for addiction-positive and addiction-negative compounds acting on the same receptors. In the chronic administration test, four out of five compounds were detected for the addiction compound, and the non-addiction compound was not misclassified as an addiction compound, suggesting that this evaluation method is capable of detecting the addiction compound. These results suggest that the evaluation system used in this study is useful as a screening system for addiction-positive compounds.