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Updated: Aug 11, 2026

Single Cell Measurement of Dopamine Release with Simultaneous Voltage-clamp and Amperometry
Published on: November 21, 2012
The neurotoxic mechanisms of amphetamine: Step by step for striatal dopamine depletion
Che-Se Tung1, Shang-Tang Chang2, Chuen-Lin Huang3
1Division of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan, ROC.
Abstract:
Amphetamine (AMPH) is a commonly abused psychostimulant that induces neuronal cell death/degeneration in humans and experimental animals. Although multiple neurotoxic mechanisms of AMPH have been intensively investigated, the interplay between these mechanisms has remained elusive. In this study, we used a rat model of AMPH-induced long-lasting striatal dopamine (DA) depletion and identified mechanisms of neurotoxicity, energy failure, excitotoxicity, and oxidative stress. Pretreatment with nicotinamide (NAM, a co-factor for the electron transport chain) blocked AMPH-induced free radical formation, energy failure, and striatal DA decrease. Also, MK-801 (a NMDA receptor antagonist) blocked AMPH-induced free radical formation and striatal DA but not energy failure decrease, indicating excitotoxicity may occur before free radical formation and after energy failure. Thus, these results show that during AMPH intoxication, energy failure, excitotoxicity, and free radical formation are orchestrated consecutively to mediate the depletion of striatal DA.
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