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 neurotox icity induced by (+/-)3,4-methylenedioxymethamphetamine (MDMA) in rats was investigiated. Pretreatment with N-omega-nitro-L-arginine (L-NOAR G) (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 othe r brain regions examined. Brain NOS activities in these two regions we re significantly elevated at 6 h after MDMA administration. Moreover, L-NOARG pretreatment caused significant inhibition of brain NOS activi ty 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 acut e monoamine changes or the hyperthermia induced by MDMA, that are resp onsible for the prevention of neurotoxicity. The regional differences on the protection of L-NOARG and on the activation of NOS by MDMA indi cate the unequal role that NO may play in MDMA-induced neurotoxicity i n different brain regions. (C) 1998 Elsevier Science B.V. All rights r eserved.