Immediate and long-term effects of 3,4-methylenedioxymethamphetamine on serotonin pathways in brain of rat.
Donna M. Stone, Kalpana M. Merchant, Glen R. Hanson, James W. Gibb
Neuropharmacology December 1987 DOI: 10.1016/0028-3908(87)90117-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | MDMA |
| Dose | 10 mg/kg; multiple doses (5 doses over a 24-hr period) |
| Duration | Up to 110 days after treatment |
| Topics | MDMA Serotonin |
| Key points | MDMA (10 mg/kg) rapidly and durably reduced markers of central serotonergic function in rats, with tryptophan hydroxylase activity falling within 15 minutes in frontal cortex and within 1 hour in other regions, and 5-HT declines following closely. Repeated dosing (5 doses over 24 hours) produced deficits lasting up to 110 days, which the authors interpret as evidence that MDMA induced destruction of serotonin-containing axon terminals. |
Abstract
In the rat, administration of the psychoactive analog of amphetamine 3,4-methylenedioxymethamphetamine (MDMA), causes selective, pronounced decreases in markers of central serotonergic function. The time course of these neurochemical changes was examined in several serotonergic nerve terminal regions of the brain. Fifteen min after subcutaneous injection of MDMA (10 mg/kg), the enzymatic activity of tryptophan hydroxylase (the rate-limiting enzyme for the biosynthesis of serotonin) was significantly decreased in the frontal cortex; by 1 hr after the injection, the activity of tryptophan hydroxylase had significantly declined in the neostriatum, hippocampus and hypothalamus as well. Although extensive recovery had occurred by 2 weeks, the activity of the enzyme remained significantly depressed in most regions. Decline of the regional content of 5-hydroxytryptamine (5-HT) closely paralleled, but was usually preceded by, that of the enzyme. Concentrations of the primary metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), were less responsive: in most regions levels of 5-HIAA had significantly decreased by 3 hr, but not by 1 hr, following treatment. Markers of dopamine function were altered transiently but had returned to control values by 24 hr. Administration of multiple doses of MDMA (5 doses over a 24-hr period) resulted in significant decreases in serotonergic parameters for up to 110 days after treatment. The rate and extent of recovery varied according to both the dose administered and the region examined. The persistence of these serotonergic deficits suggests that MDMA induced the destruction of serotonin-containing axon terminals.