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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000153-10
Application #
6987718
Study Section
(CNRB)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2004
Total Cost
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Wang, Yun; Chang, Chen-Fu; Chou, Jenny et al. (2005) Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage. Exp Neurol 193:75-84
Chen, Jia; Lee, Chun-Ting; Errico, Stacie et al. (2005) Protective effects of Delta(9)-tetrahydrocannabinol against N-methyl-d-aspartate-induced AF5 cell death. Brain Res Mol Brain Res 134:215-25
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Sokolov, Boris P; Schindler, Charles W; Cadet, Jean Lud (2004) Chronic methamphetamine increases fighting in mice. Pharmacol Biochem Behav 77:319-26
Yu, Jing; Wang, Jing; Cadet, Jean Lud et al. (2004) Histological evidence supporting a role for the striatal neurokinin-1 receptor in methamphetamine-induced neurotoxicity in the mouse brain. Brain Res 1007:124-31
Bolla, K I; Eldreth, D A; London, E D et al. (2003) Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task. Neuroimage 19:1085-94
Rothman, Richard B; Jayanthi, Subramaniam; Wang, Xiaoying et al. (2003) High-dose fenfluramine administration decreases serotonin transporter binding, but not serotonin transporter protein levels, in rat forebrain. Synapse 50:233-9
Noailles, Pierre Antoine H; Becker, Kevin G; Wood 3rd, William H et al. (2003) Methamphetamine-induced gene expression profiles in the striatum of male rat pups exposed to the drug in utero. Brain Res Dev Brain Res 147:153-62
Contoreggi, Carlo; Herning, Ronald I; Na, Paul et al. (2003) Stress hormone responses to corticotropin-releasing hormone in substance abusers without severe comorbid psychiatric disease. Biol Psychiatry 54:873-8
Lyles, Johnalyn; Cadet, Jean Lud (2003) Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms. Brain Res Brain Res Rev 42:155-68

Showing the most recent 10 out of 19 publications