A single dose of MDMA (15 mg/kg) in male Dark Agouti rats caused lasting damage to the serotonin system, shown by 30–60% reductions in paroxetine binding in the forebrain and decreased brain glucose metabolism in aggression-related areas. Despite this neurotoxicity, aggressive behaviors (biting, boxing, wrestling) were not significantly different from controls three weeks later, and the acute anti-aggressive effects of MDMA and two 5-HT1B receptor agonists remained intact. The findings suggest that aggressive behavior and the acute anti-aggressive action of MDMA are preserved even with substantial serotonergic damage, at least under the social isolation conditions of the resident-intruder test.
A single dose of MDMA causes long-term loss of serotonin nerve terminals and disrupts the normal coupling between brain blood flow and glucose use. Three weeks after MDMA pretreatment in rats, serotonin transporter density fell by about 46% and paroxetine binding by 47%. Brain glucose use decreased widely, but blood flow did not change, indicating lost cerebrovascular constrictor tone. A subsequent MDMA dose increased glucose use but decreased blood flow overall; in half of pretreated rats, random focal hyperemia suggested a failure of autoregulation during MDMA-induced hypertension. The findings suggest that prior MDMA exposure does not protect against acute cerebrovascular dysfunction and may, in some individuals, increase stroke risk.