Neural Effects of MDMA as Determined by Functional Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy in Awake Marmoset Monkeys
Jerrold S. Meyer, Matthew E. Brevard, Brian J. Piper, Syed F. Ali, Craig F. Ferris
Annals of the New York Academy of Sciences August 1, 2006 DOI: 10.1196/annals.1369.036
Summary
A recreational dose of MDMA (1 mg/kg) significantly activates brain regions in marmoset monkeys, including the amygdala and hippocampus. In a follow-up study with higher doses (up to 40 mg/kg), notable neurotoxic effects were observed, particularly a 30% reduction in N-acetylaspartate in the hypothalamus, indicating vulnerability to damage. Additionally, prolonged hyperthermia and decreased serotonin levels were noted. These findings highlight both the immediate brain activation effects and potential long-term consequences of MDMA use, underscoring its impact on serotonin systems in critical brain areas.
Abstract
Abstract: We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of a recreational dose (1 mg/kg p.o.) of 3,4‐methylenedioxymethamphetamine (MDMA) on regional brain activity in awake, restrained marmoset monkeys. In a second study, magnetic resonance spectroscopy (MRS) and postmortem measurements of serotonin transporter (SERT) binding and serotonin (5‐HT) concentrations were used to determine the neurotoxic effects of low (4 × 1 mg/kg p.o.) and high (4 × 10 mg/kg i.m.) doses of MDMA. Several brain areas were significantly activated by the low oral dose of MDMA, including the midbrain raphe nuclei, hippocampus, hypothalamus, amygdala, and the corticostriatal circuit composed of the dorsal thalamus, sensory motor cortex, and basal ganglia. MDMA activated the primary visual cortex under baseline conditions and also enhanced the visual cortical response to photic stimulation. The onset of brain activation correlated well with the rise in plasma MDMA concentrations measured in separate monkeys given the same drug treatment. In the second study, the ratio of N ‐acetylaspartate (NAA; a putative neuronal marker) to creatine was significantly reduced in the hypothalamus following either MDMA treatment regimen, suggesting a particular vulnerability of this structure to MDMA‐induced damage. Monkeys given the high‐dose regimen also showed prolonged hyperthermia and reductions in 5‐HT and SERT in a number of brain areas. These results are the first to identify the pattern of MDMA‐induced brain activation in a nonhuman primate model, and they further suggest that even recreational doses of MDMA may have adverse consequences as indicated by the reduced hypothalamic NAA/creatine ratio.