Microelectrode Array Biochip: Tool for In Vitro Drug Screening Based on the Detection of a Drug Effect on Dopamine Release from PC12 Cells

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Abstract
Novel, yet simple detection techniques of drug effect, including the effect of a vesicular monoamine transporter inhibitor (reserpine), a dopamine precursor (l-dopa), and a dopamine transporter inhibitor (nomifensine), on dopamine release from dopaminergic PC12 cells were developed based on a microelectrode array (MEA) biochip. Upon multi-injections of KCl solution into the culture of PC12 cells attached on a MEA biochip, the K+-stimulated dopamine release was temporally and amperometrically recorded by biochip microelectrodes. Two parameters in the recorded amperometric spectra were defined in this study: the peak current of the first KCl injection (Max1), and the steady current after the fourth KCl injection (St4). Statistically significant effects of l-dopa and reserpine were demonstrated by comparing both Max1 and St4 of the second detections in drugs with those of the control without drug treatment. The values of both Max1 and St4 in the first detections were normalized as 1. In contrast, the statistically significant effect of nomifensine was detected by comparing the ratios of St4 to Max1 in the first detections in drug with those of the control. The reason for using different analytical methods for measurements between l-dopa/reserpine and nomifensine lies in the different mechanisms of action on PC12 cells among these drugs. The novel analytical methods developed use the same detection setup and parameters, and the data analysis for the effect of drugs becomes simple. The methods hence may provide a high-throughput in vitro drug screening approach for dopamine-related psychiatric disorders.

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