Analysis of Ecstasy (MDMA)‐induced transcriptional responses in the rat cortex
Bruce Ladenheim, Michael Mccoy, Jean Lud Cadet, Nathalie Thiriet
The FASEB Journal December 1, 2002 DOI: 10.1096/fj.02-0502com via OpenAlex
Summary
AI-generated from the abstractMDMA (ecstasy) triggers changes in gene activity in the rat cortex within hours of a single injection. The genes affected are involved in signaling, transcription regulation, and xenobiotic metabolism, suggesting that the cortex responds acutely by altering transcription of genes that could lead to long-term brain changes. MDMA is known to cause hyperthermia, reactive oxygen species, and long-term serotonin depletion, with the cortex especially sensitive. These molecular changes may underlie the drug's lasting effects on the brain.
Study at a glance
| Characteristics | Experimental study using cDNA array analysis Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | MDMA injection |
| Dose | a single dose |
| Topics | MDMA Serotonin |
| Keywords | Euphoriant Hallucinogen Neurotoxicity |
| Citations | 34 |
| Key finding | A single MDMA injection in rats modulates transcription of genes encoding signaling, transcription regulator, and xenobiotic metabolism proteins in the cortex. |
Abstract
ABSTRACT 3,4‐Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular drug of abuse. MDMA is pharmacologically classified as an entactogen because of its affinities to classical hallucinogens and stimulants. Oral ingestion of a single dose of the drug is associated with euphoria, elevated self‐confidence, and heightened sensory awareness in humans. Evidence for neurotoxicity in the human serotonin (5‐HT) system has been provided. In rats, a single injection of MDMA induces hyperthermia and formation of reactive oxygen species. These effects may cause MDMA‐associated, long‐term 5‐HT depletion, with the cortex being quite sensitive to the biochemical effects of MDMA. It has been suggested that these MDMA effects may be associated with molecular changes in this brain region. To test these ideas, we have made use of the cDNA array analysis, which can provide a more global view of the molecular changes secondary to MDMA injections. Our results show that the genes regulated by MDMA encode proteins that belong to signaling pathways, transcription regulators, or xenobiotic metabolism. Our observations indicate that cortical cells respond to the acute administration of MDMA by modulating transcription of several genes that might lead to long‐term changes in the brain.—Thiriet, N., Ladenheim, B., McCoy, M. T., Cadet, J. L. Analysis of Ecstasy (MDMA) ‐induced transcriptional responses in the rat cortex. FASEB J. 16, 1887–1894 (2002)