Low striatal serotonin transporter protein in a human polydrug MDMA (ecstasy) user: a case study
Journal of Psychopharmacology – October 02, 2008
Source: OpenAlex
Summary
High-dose MDMA use may lead to significant damage in brain serotonin neurons. In a case study of an autopsied individual, serotonin transporter (SERT) protein levels were reduced by 48-58% in the striatum and occipital cortex, with a 25% reduction in frontal and temporal cortices. Additionally, tryptophan hydroxylase (TPH), crucial for serotonin synthesis, showed drastic declines of 68% and 95% in the caudate and putamen, respectively. These findings suggest potential physical damage or downregulation in serotonin neuron components due to MDMA exposure.
Abstract
Evidence that the widely used methamphetamine analog MDMA (3,4-methylenedioxymethamphetamine, ecstasy) might damage brain serotonin neurones in humans is derived from imaging investigations showing variably decreased binding of radioligands to the serotonin transporter (SERT), a marker of serotonin neurones. However, in humans, it is not known whether low SERT binding reflects actual loss of SERT protein itself. As this question can only be answered in post-mortem brain, we measured protein levels of SERT and that of the rate-limiting serotonin-synthesizing enzyme tryptophan hydroxylase (TPH) in autopsied brain of a high-dose MDMA user. As compared with control values, SERT protein levels were markedly (−48% to −58%) reduced in striatum (caudate, putamen) and occipital cortex and less affected (−25%) in frontal and temporal cortices, whereas TPH protein was severely decreased in caudate and putamen (−68% and −95%, respectively). The magnitude of the striatal SERT protein reduction was greater than the SERT binding decrease typically reported in imaging studies. Although acknowledging limitations of a case study, these findings extend imaging data based on SERT binding and suggest that high-dose MDMA exposure could cause loss of two key protein markers of brain serotonin neurones, a finding compatible with either physical damage to serotonin neurones or downregulation of components therein.