N&PD Moderators: Skorpio | someguyontheinternet
The mechanism by which 3,4-methylenedioxymethamphetamine (MDMA) produces serotonin (5-HT) neurotoxicity is unknown but considerable evidence suggests that endogenous brain dopamine (DA) is involved. However, it has recently become apparent that some of the data implicating brain DA in MDMA neurotoxicity may be confounded by drug effects on thermoregulation. The purpose of the present studies was to examine the role of DA in MDMA neurotoxicity, while controlling for possible confounding effects of drug- induced changes in core temperature. Rats were treated with reserpine, alone and in combination with alpha-methyl-p -tyrosine (AMPT), to deplete vesicular and cytoplasmic stores of DA. When drug-induced hypothermia was averted (by raising ambient temperature), the 5-HT neuroprotective effects of reserpine and AMPT were no longer apparent. The lack of neuroprotection by AMPT and reserpine, alone and in combination, in studies that control for the effects of these drugs on core temperature, suggests that DA per se is not essential for the expression of MDMA-induced 5-HT neurotoxicity.
Yuan J, Cord BJ, McCann UD, Callahan BT, Ricaurte GA "Effect of depleting vesicular and cytoplasmic dopamine on MDMA neurotoxicity", J Neurochem, 2002; 80(6):960-9
In 2002, an important new piece of research was done: Animals who had been given drugs that removed virtually all of the serotonin and dopamine in their brains were given what should have been a neurotoxic dose of MDMA. And nothing happened. There was no damage.[3] At first, it seemed as though the 'dopamine' camp had been right. However, the scientists noticed that something else was different in these dopamine depleted animals: When they gave them the overdose of MDMA, they didn't overheat as expected.
That was significant, because past research had shown that overheating was the key to MDMA neurotoxicity. It wasn't enough to give an animal a massive dose of MDMA; if the body's protective mechanisms weren't impaired by overheating, the animal could usually cope and did not suffer damage. Knowing this, the researchers took another group of dopamine depleted animals, gave them another overdose of MDMA, and warmed them with heating pads so that their temperature reached the same levels as normal (control) animals did when given the same ammount of MDMA. The results were striking: The animals with essentially no dopamine in their brains suffered the same level of neurotoxic damage as the control animals did when their body temperatures were kept as high. Something else was at work; dopamine was not the toxic chemical in question. (Ironically, dopamine and norepinephrine release appears to still be important in MDMA neurotoxicity because it promotes activity/heat production, increasing the risk of overheating (which in turn seems to greatly increase the risk of neurotoxicity.))