Self‐administered MDMA produces dose‐ and time‐dependent serotonin deficits in the rat brain
Addiction Biology September 28, 2011 DOI: 10.1111/j.1369-1600.2011.00370.x via OpenAlex
Summary
AI-generated from the abstractMDMA use is rising worldwide, and high doses reduce serotonin (5HT) markers in the brain. This study examined whether self-administered MDMA causes lasting serotonin deficits in rats. Rats self-administered MDMA infusions until reaching total doses of either 165 or 315 mg/kg. Serotonin levels in the frontal cortex, striatum, and hippocampus were measured 2 or 10 weeks later. The lower dose did not significantly reduce serotonin in any brain region. The higher dose decreased serotonin by 30–35% in all three regions at 2 weeks, but levels recovered by 10 weeks. These dose- and time-dependent deficits suggest similar effects may occur in humans who use MDMA.
Study at a glance
| Characteristics | Laboratory experiment Peer reviewed |
|---|---|
| Population | Laboratory rats |
| Dose | 1.0 mg/kg/infusion initially, reduced to 0.5 mg/kg/infusion after 90 infusions; total doses of 165 or 315 mg/kg self-administered |
| Duration | Self-administration until total doses reached; assays at 2 or 10 weeks after last session |
| Topics | MDMA Serotonin |
| Keywords | Neuroscience Psychology |
| Citations | 37 |
| Key finding | Self-administered MDMA at a total dose of 315 mg/kg reduced serotonin levels by 30–35% in the frontal cortex, striatum, and hippocampus at 2 weeks, but not at 10 weeks, while a lower dose of 165 mg/kg produced no significant deficits. |
Abstract
ABSTRACT 3,4‐Methylenedioxymethamphetamine (MDMA) use and abuse have been increasing worldwide. Of concern, exposure to high doses of MDMA decreases several markers of serotonin (5HT) neurotransmission and produces deficits in tissue levels of 5HT. Studies in laboratory animals have been conducted primarily following large doses (20.0–80.0 mg/kg) of experimenter‐administered MDMA, but it is unclear whether similar persistent deficits in tissue 5HT levels are produced following self‐administration. In this study, tissue levels of 5HT in the frontal cortex, striatum and hippocampus were measured following different levels of self‐administered MDMA. For both groups, responding was initially reinforced by an infusion of 1.0 mg/kg/infusion MDMA. The dose was reduced to 0.5 mg/kg/infusion once 90 infusions had been self‐administered. For the two groups, testing continued until either a total of 165 or 315 mg/kg had been self‐administered. Assays were conducted either 2 or 10 weeks following the last self‐administration session. The lower dose exposure regimen failed to significantly decrease 5HT levels in any brain region. The higher dose exposure, however, decreased 5HT levels by 30–35% in all three brain regions 2 weeks, but not 10 weeks, following self‐administration. Thus, MDMA self‐administration produced dose‐ and time‐dependent deficits in tissue levels of 5HT, suggesting that similar deficits would be produced in humans who use and abuse the drug.