The role of monoamine oxidase B (MAO-B) in MDMA neurotoxicity was tested in rats via central administration of vehicle or antisense oligonucleotide (AS ODN) against rat MAO-B via minipump prior to and during MDMA administration. (AS ODN administered for 7 days pre-MDMA). Rats were sacrificed 7 days after the administration of 40 mg/kg MDMA or saline, and neurotransmitter concentration was measured in striatal tissue via HPLC, including measures of tissue 5-HT, 5-HIAA, DA and DOPAC. Rats given AS ODN against MAO-B before MDMA had significantly higher concentrations of striatal 5-HT and 5HIAA compared with rats given MDMA alone, and AS ODN pretreatment did not reduce MDMA-induced hyperthermia. Another experiment wherein DA release was measured via microdialysis after 10 mg/kg MDMA indicated that anti-MAO-B AD ODN also did not reduce direct DA release, but DA turnover was reduced. In vitro studies of the antisense nucleotide indicate that it inhibited rat MAO-B. Research findings support Nichols' hypotheses concerning the causes of MDMA serotonergic neurotoxicity, which views DA metabolism and the production of hydrogen peroxide as the culprit. While it seems unlikely that anti-MAO-B AS ODN possesses anti-oxidant properties, or that the continued absence of MAO-B could modulate endogenous antioxidant systems, no tests were performed to examine these possibilities. These findings stand opposed to reports by Colado (1999) and Yuan (2001) that dopamine and its metabolites are not associated with MDMA neurotoxicity. Implications for humans are unclear, though such findings suggest that taking precursors to dopamine (such as L-tyrosine) or psychostimulants before MDMA may increase risk of reducing serotonin function.