Sorry for copy pasta
"When l-DOPA was given 2 h after MDMA we observed that extracellular dopamine was increased above that seen in the MDMA alone treated group for approximately 3 h and that HVA and DOPAC concentrations also increased markedly over a similar period. These changes presumably reflect increased dopamine synthesis and release. Despite this clear in vivo indication of increased dopamine release and possibly also function, no enhancement of MDMA neurotoxicity was observed 7 days later. These data are in contradiction of the report of Schmidt et al. (1991) that MDMA-induced neurotoxicity is enhanced by l-DOPA. While Schmidt and colleagues used higher doses of l-DOPA these proved impossible to administer in the current study as they proved fatal. This is probably because of the use of the Dark Agouti strain of rat in our study since we have previously found that neurotoxicity occurs in these animals after much lower doses of MDMA and p-chloroamphetamine (PCA) than are required with other strains (see Colado et al., 1995; 1997b; Murray et al., 1996). Nevertheless using the highest practical dose of l-DOPA, no potentiation of MDMA-induced toxicity was detected. We were also unable to induce neurotoxicity in rats given a sub-toxic dose of MDMA by also administering l-DOPA, as was also reported by Schmidt et al. (1991).
In order to investigate further this apparent discrepancy between our data and that of Schmidt et al. (1991) we also examined whether l-DOPA altered MDMA-induced free radical formation. The MDMA-induced increase in the dialysate concentration of 2,3-and 2,5-DHBA that has previously been reported to occur after MDMA administration (Colado et al., 1997b; 1998c) was again seen in the current study. While the concentration of 2,5-DHBA appeared to be increased by l-DOPA, this change was not statistically significant. In any event, as Halliwell et al. (1991) have pointed out, a 2,3-DHBA increase is the only reliable indicator of increased free radical formation because of enzyme-induced conversion of salicylate to 2,5-DHBA. Nevertheless we found no evidence that the MDMA-induced increase in either 2,3- or 2,5-DHBA was even modestly enhanced by l-DOPA administration. Thus one plausible explanation for the results obtained by Schmidt et al. (1991), namely that tissue damage resulting from free radicals produced by MDMA metabolism (see Colado et al., 1997b) would be further potentiated by administration of l-DOPA, a compound that through its metabolism to dopamine would also increase free radical production through auto-oxidation (see Chiueh et al., 1992; 1993), could not be supported.
What does remain a possible explanation for the discrepant findings is the degree of hyperthermia produced by addition of l-DOPA to MDMA-treated rats. As we and others have shown, sustained hyperthermia markedly enhances the neurotoxic damage produced by MDMA (Colado et al., 1998b; Broening et al., 1995) presumably because hyperthermia is conducive to enhancing free radical production (Kil et al., 1996). If l-DOPA produced a sustained hyperthermia in the strain of rats used by Schmidt et al. (1990) rather than the more transient effect we observed, then neurotoxic damage would probably be increased. However, such a mechanism does not indicate that dopamine has a core role in MDMA-induced neurodegeneration as has been proposed by others (Stone et al., 1988; Schmidt et al., 1991). In this regard it is also worth pointing out that in our current study the increase in extracellular dopamine was almost the same whether a neurotoxic dose of MDMA of 15 mg kg−1 or a non-toxic dose of 5 mg kg−1 was given."
Seems like there are some issues with replications concerning that particular species of rat... But at any rate it does seem to lessen the likeliness that dopamine uptake into serotonin nerve terminals is playing a big role in terminal loss.
But I'm still confused as to why MAO-B inhibition is so protective if that is the case. Does MAO-B break down those MeDA metabolites of MDMA then or something? Or does MAO-B alter physiology in some other way that lessens uptake of MDMA metabolites or lessens the harmfulness of those MDMA metabolites?
