Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway

SPECIFIC AIMSAmphetamine (AMPH) is a psychostimulant whose chronic abuse may cause impairment in attention and memory in humans. These cognitive deficits might be related to neurotoxic effects of the drug. A well-known toxic effect of AMPH is the degeneration of striatal dopamine (DA) terminals. The purpose of this study was to investigate the hypothesis that AMPH might cause neuronal apoptosis via activation of the mitochondria-dependent cell death pathway.PRINCIPAL FINDINGS1. AMPH causes apoptosis and reactive astrocytosis in the striatumTo clarify whether AMPH administration can cause apoptosis in the striatum, we used a TUNEL technique to assay for DNA fragmentation. Very few TUNEL-positive cells were seen in the striata of saline-treated mice. However, administration of the drug (10 mg/kg, 4 times, every 2 h, which causes significant damage to DA terminals) induced increases in TUNEL-positive staining in nondopaminergic cells in the striatum (Fig. 1⤻ A). Quantification of these changes 1–7 days after...