Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway Irina N. Krasnova, Bruce Ladenheim and Jean Lud Cadet 1 Molecular Neuropsychiatry Branch, NIDA-IRP, DHHS/NIH, Baltimore, Maryland, USA 1 Correspondence: Molecular Neuropsychiatry Branch, DHHS/NIH/NIDA, 5500 Nathan Shock Dr., Baltimore, MD 21224, USA. Email: jcadet@intra.nida.nih.gov <h3>SPECIFIC AIMS</h3> Amphetamine (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. <h3>PRINCIPAL FINDINGS</h3> <h3>1. AMPH causes apoptosis and reactive astrocytosis in the striatum</h3> To 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 (<h3>Fig. 1</h3> A). Quantification of these changes
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Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway
Krasnova, Irina N.; Ladenheim, Bruce; Cadet, Jean Lud
Follow The FASEB Journal
, Volume 19 (7): 851
Fed of American Socs for Experimental Biology – May 1, 2005
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