Synapse
January 1, 2000
Richard B. Rothman, Michael H. Baumann, Christina M. Dersch et al.
933 citations
Stimulants like amphetamine, MDMA, and methamphetamine are known to produce reinforcing effects in animals through the brain chemical dopamine. However, their subjective effects in humans—such as euphoria or alertness—may rely more on norepinephrine. Using lab tests, the authors measured how several stimulants affect the release of norepinephrine and dopamine. They found that all tested drugs were most potent at releasing norepinephrine. Crucially, the oral doses that produce amphetamine-like subjective effects in people correlated with the drugs' ability to release norepinephrine, not dopamine, and did not lower prolactin levels (a marker of dopamine release). These findings suggest norepinephrine may play a key role in the subjective experience of stimulants in humans.
Psychopharmacology
March 15, 2006
Michael H. Baumann, Xiaoying Wang, Richard B. Rothman
269 citations
High doses of MDMA (ecstasy) reduce serotonin levels in the brains of rats, but this reduction does not necessarily indicate that neurons have been damaged. The drug works by stimulating the release of serotonin, norepinephrine, and dopamine. At doses that cause long-term serotonin depletion (10-20 mg/kg), markers of actual neuronal damage such as cell death or gliosis are not reliably increased. Even moderate doses that do not deplete serotonin can produce lasting anxiety-like behaviors in rats, suggesting potential risks from the drug beyond neurotoxicity.
Synapse
July 14, 2004
Xiaoying Wang, Michael H. Baumann, Heng Xu et al.
101 citations
Two weeks after giving rats MDMA (7.5 mg/kg, three doses) or the toxin 5,7-DHT, the study measured serotonin levels and two protein markers in brain regions. MDMA reduced tissue serotonin by about 50% in cortex, hippocampus, and caudate but did not significantly change the amount of serotonin transporter or glial fibrillary acidic protein, a marker of nerve damage. In contrast, 5,7-DHT reduced serotonin by over 90%, lowered serotonin transporter protein by 20–35%, and increased glial fibrillary acidic protein by 30–39%. The authors conclude that this MDMA regimen does not cause degeneration of serotonin nerve terminals and that lasting serotonin depletion can occur without destroying the axons.
Synapse
October 1, 1995
Jean Lud Cadet, Bruce Ladenheim, Hiroshi Hirata et al.
81 citations
Mice carrying extra copies of the human superoxide dismutase gene are protected against MDMA-induced damage to brain dopamine neurons. Normal mice showed large drops in striatal dopamine and its metabolite DOPAC one day and two weeks after a single MDMA injection. Mice with one copy of the transgene showed dopamine loss only at one day, while mice with two copies showed no loss at either time point. Three repeated injections caused dopamine loss in normal mice, small losses in one-copy mice, and no loss in two-copy mice. Serotonin levels were unaffected in all groups. The findings indicate that superoxide radicals contribute to MDMA's dopamine toxicity.
Drug Metabolism and Disposition
October 19, 2013
Marta Concheiro, Michael H. Baumann, Karl B. Scheidweiler et al.
32 citations
MDMA, an illicit drug with potential clinical use for PTSD and anxiety, shows nonlinear accumulation in male rats due to metabolic autoinhibition. After doses of 2.5, 5, and 10 mg/kg, MDMA and its metabolite MDA increased more than proportionally with dose, while other metabolites remained constant. Serotonin syndrome severity correlated with MDMA concentrations, and core temperature correlated with MDA concentrations, suggesting distinct mechanisms for behavioral and hyperthermic effects. At 2.5 mg/kg, MDMA Cmax was 164 ± 47.1 ng/ml, with HHMA and HMMA as major metabolites and less than 20% converted to MDA. These findings, given similarities to human pharmacokinetics, support using rat data at clinically relevant doses.
Annals of the New York Academy of Sciences
May 1, 1998
Michael H. Baumann, Richard B. Rothman, Syed F. Ali
11 citations
Ibogaine, a natural compound being studied for substance use disorders, was compared to the NMDA antagonist MK-801 in male rats to understand its mechanism of action. Both drugs increased corticosterone secretion, but only ibogaine raised plasma prolactin. Ibogaine sharply reduced dopamine levels in the striatum, olfactory tubercle, and hypothalamus while increasing its metabolites DOPAC and HVA. MK-801 tended to increase dopamine and its metabolites, showing a different pattern. Neither drug affected serotonin systems. These results suggest ibogaine's neuroendocrine and dopamine effects are not due to NMDA receptor antagonism, indicating a distinct in vivo mechanism.