Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine.
Journal of Pharmacology and Experimental Therapeutics 1987 DOI: 10.1016/s0022-3565(25)22673-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats (implied by typical neurochemical study context) |
| Interventions | MDMA fluoxetine |
| Duration | Up to 1 week after drug administration |
| Topics | MDMA Serotonin |
| Keywords | P-chloroamphetamine Pharmacology Neurochemical Fluoxetine Neurotoxicity Endocrinology |
| Citations | 530 |
| Key findings | MDMA causes a biphasic depletion of cortical serotonin, with a reversible acute phase and a later neurotoxic phase specific to the (+)-stereoisomer, which can be blocked by fluoxetine. |
Abstract
The neurochemical effects of the unique psychedelic agent, methylenedioxymethamphetamine (MDMA), indicate it may be a serotonergic neurotoxin related to agents such as p-chloroamphetamine. MDMA had a biphasic effect on cortical serotonin concentrations beginning with an acute depletion of the transmitter which reached a maximum between 3 and 6 hr after drug administration. This early phase of depletion was reversible because cortical serotonin concentrations had recovered to control levels by 24 hr. However, transmitter concentrations were reduced significantly 1 week later, indicating a second phase of depletion. The latter phase of depletion was associated with a decrease in synaptosomal [3H]serotonin uptake due to a loss in the number of uptake sites with no change in the affinity of the carrier for serotonin. This neurotoxic effect of MDMA was found to be a property of the (+)-stereoisomer of the drug as only this enantiomer produced the depletion of cortical serotonin and the decrease in synaptosomal serotonin uptake at 1 week. In contrast to this, both stereoisomers of the drug could produce the acute depletion of cortical serotonin measured 3 hr after drug administration. Coadministration of the selective serotonin uptake inhibitor, fluoxetine, completely blocked the reduction in cortical serotonin concentrations 1 week after MDMA. Administration of fluoxetine at various times after MDMA revealed that the long-term effects of the drug developed independently of the acute depletion of serotonin and could be partially blocked by the uptake inhibitor as long as 6 hr after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)