Role of brain nitric oxide in (+/-)3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity in rats.
The role of nitric oxide (NO) in the long-term serotoninergic neurotoxicity induced by (+/-)3,4-methylenedioxymethamphetamine (MDMA) in rats was investigiated. Pretreatment with Nomega-nitro-L-arginine (L-NOARG) (10 mg kg-1), a nitric oxide synthase (NOS) inhibitor, partially protected against long-term serotonin (5-HT) depletion induced by MDMA (40 mg kg-1) in frontal cortex and parietal cortex, but not in other brain regions examined. Brain NOS activities in these two regions were significantly elevated at 6 h after MDMA administration. Moreover, L-NOARG pretreatment caused significant inhibition of brain NOS activity but did not affect the acute 5-HT and dopamine (DA) changes or the hyperthermia induced by MDMA. These results suggest that it is the NOS inhibitory properties of L-NOARG, rather than its effects on the acute monoamine changes or the hyperthermia induced by MDMA, that are responsible for the prevention of neurotoxicity. The regional differences on the protection of L-NOARG and on the activation of NOS by MDMA indicate the unequal role that NO may play in MDMA-induced neurotoxicity in different brain regions.
Zheng
Y
Y
Department of Pharmacology, University of Otago, P.O. Box 913, Dunedin, New Zealand.
Laverty
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R
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000633:toxicity*
D004791:Enzyme Inhibitors; D007191:Indazoles; D009419:Nerve Tissue Proteins; D018490:Serotonin Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C080122:7-nitroindazole