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INVOLVEMENT OF OXIDATIVE AND L-ARGININE-NO PATHWAYS IN THE NEUROTOXICITY OF DRUGS OF ABUSE IN VITRO |
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| Authors: | C Cerruti P Sheng B Ladenheim C J Epstein† J-L Cadet |
| Institution: | *Molecular Neuropsychiatry Section, NIHI NIDA/ Division of Intramural Research, Baltimore, Maryland and;†Department of Pediatrics, University of California, San Francisco, California, USA |
| Abstract: | 1. Inhibitors of nitric oxide (NO) formation or ADP-ribosylation attenuate methamphetamine (METH)- and methyl-enedioxymetamphetamine (MDMA)-induced neurotoxicity on dopaminergic and serotonergic cells in primary cultures. 2. They also prevent METH-induced reactive gliosis in dopaminergic cultures. 3. Overexpression of superoxide dismutase (SOD) in cells obtained from SOD-transgenic mice also attenuates drug-induced toxicity. 4. These data indicate a role for oxygen-based and NO free radicals in the mechanisms of cell death associated with drugs of abuse in vitro. |
| Keywords: | methamphetamine methylenedioxymetamphet-amine nitric oxide synthase oxidative stress primary cultures superoxide dismutase-transgenic mice |