Resumen de Response to O'Shea and Colado: the MDMA neurotoxicity profile might provide clues to mechanisms.: the MDMA neurotoxicity profile might provide clues to mechanisms.
George A. Ricaurte, Jie Yuan, George Hatzidimitriou, Branden J. Cord, Una D. McCann
We commend O'Shea and Colado for their thoughtful commentary [ 1 ] on our recent study [ 2 ]. They raise the interesting possibility that very small increments in temperature, even if within the typical range routinely used to house non-human primates, could be responsible for the emergence of neurotoxicity to dopamine (DA)-containing neurons in animals treated with a sequential dose regimen of 3,4-methylenedioxymethamphetamine (MDMA). Previous studies in non-human primates housed at various different temperatures have not demonstrated graded increases of toxicity to DA-containing neurons [ 3 , 4 , 5 , 6 , 7 ] but, rather, selective toxicity to serotonin (5-HT)-containing neurons. However, as noted in our study [ 2 ], it is possible that DA-containing neurons, once affected by sequential dosing, are more sensitive to temperature-related increases in neurotoxicity than are 5-HT-containing neurons. This possibility was raised by previous findings in rodents [ 8 ] suggesting that DA-containing neurons, when compared with 5-HT-containing neurons, were more sensitive to temperature increases following treatment with methamphetamine. Studies are currently underway to evaluate this possibility in primates. If it is determined that small temperature changes within typical ambient ranges can profoundly influence the effects of MDMA on DA-containing neurons in non-human primates, this would have significant implications for humans who employ a repeated-dosing regimen in settings where temperatures can vary widely.
