A PET study of effects of chronic 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) on serotonin markers in Göttingen minipig brain
Synapse – April 05, 2007
Source: OpenAlex
Summary
MDMA, commonly known as ecstasy, significantly decreases serotonin transporter levels in the brains of Göttingen minipigs. Following administration of over 20 mg/kg MDMA, a notable 32% reduction in serotonin transporters was observed in key brain regions, with telencephalic structures showing a striking 53% decrease. Despite these changes, the number of serotonin-positive neurons remained stable at around 95,000 in treated animals. Interestingly, no consistent alterations were found in serotonin 5HT1A receptor binding, highlighting complex neurochemical interactions following MDMA exposure.
Abstract
Abstract The psychostimulant 3,4‐methylendioxymethamphetamine (MDMA, “ecstasy”) evokes degeneration of telencephalic serotonin innervations in rodents, nonhuman primates, and human recreational drug users. However, there has been no alternative to nonhuman primates for studies of the cognitive and neurochemical consequences of serotonin depletion in a large‐bodied animal. Therefore, we used positron emission tomography (PET) with [ 11 C]DASB to map the distribution of plasma membrane serotonin transporters in brain of Göttingen minipigs, first in a baseline condition, and again at 2 weeks after treatment with MDMA (i.m.), administered at a range of doses. In parallel PET studies, [ 11 C]WAY‐100635 was used to map the distribution of serotonin 5HT 1A receptors. The acute MDMA treatment in awake pigs evoked 1°C of hyperthermia. MDMA at total doses greater than 20 mg/kg administered over 2–4 days reduced the binding potential (pB) of [ 11 C]DASB for serotonin transporters in porcine brain. A mean total dose of 42 mg/kg MDMA in four animals evoked a mean 32% decrease in [ 11 C]DASB pB in mesencephalon and diencephalon, and a mean 53% decrease in telencephalic structures. However, this depletion of serotonin innervations was not associated with consistent alterations in the binding of [ 11 C]WAY‐100635 to serotonin 5HT 1A receptors. Stereological cell counting of serotonin‐positive neurons, which numbered 95,000 in the dorsal raphé nucleus of normal animals, was unaffected in MDMA‐treated group. group. Synapse 61:478–487, 2007. © 2007 Wiley‐Liss, Inc.