Methamphetamine-induced neuronal apoptosis involves the activation of multiple death pathways. Review.
The abuse of the illicit drug methamphetamine (METH) is a major concern because it can cause terminal degeneration and neuronal cell death in the brain. METH-induced cell death occurs via processes that resemble apoptosis. In the present review, we discuss the role of various apoptotic events in the causation of METH-induced neuronal apoptosis in vitro and in vivo. Studies using comprehensive approaches to gene expression profiling have allowed for the identification of several genes that are up-regulated or down-regulated after an apoptosis-inducing dose of the drug. Further experiments have also documented the fact that the drug can cause demise of striatal enkephalinergic neurons by cross-talks between mitochondria-, endoplasmic reticulum- and receptor-mediated apoptotic events. These neuropathological observations have also been reported in models of drug-induced neuroplastic alterations used to mimic drug addiction (Nestler, 2001).
Cadet
Jean Lud
JL
Molecular Neuropsychiatry Branch, NIH/NIDA, Intramural Research Program, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. JCADET@intra.nida.nih.gov
Jayanthi
Subramaniam
S
Deng
Xiaolin
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004721:Endoplasmic Reticulum / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects; D023421:Models, Animal; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism
D000697:Central Nervous System Stimulants; D014157:Transcription Factors; D008694:Methamphetamine