Ethanol increases the distribution of MDMA to the rat brain: possible implications in the ethanol-induced potentiation of the psychostimulant effects of MDMA
Sami Ben Hamida, Antoine Tracqui, Anne Pereira De Vasconcelos, E. Szwarc, Christine Lazarus, Christian Kelche, Byron C Jones, Jean-Christophe Cassel
The International Journal of Neuropsychopharmacology December 2, 2008 DOI: 10.1017/s1461145708009693 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA ethanol |
| Dose | 6.6 or 10 mg/kg MDMA with or without 1.5 g/kg ethanol |
| Duration | 5, 15, or 60 minutes after injection |
| Topics | MDMA |
| Keywords | Pharmacology Microdialysis Striatum Neurotoxicity Hippocampus Long-term potentiation Ethanol Dopamine |
| Citations | 27 |
| Key findings | Ethanol increases brain and blood concentrations of MDMA in rats, which may contribute to the potentiation of MDMA-induced hyperactivity and could enhance neurotoxicity and abuse liability. |
Abstract
Ecstasy (3,4-methylenedioxymethylamphetamine; MDMA) is a popular club drug often taken with ethanol (EtOH). We recently found EtOH potentiated the psychomotor effects of MDMA in rats. This potentiation could reflect pharmacodynamic or/and pharmacokinetic processes. To test the latter hypothesis, rats were injected i.p. with 6.6 or 10 mg/kg MDMA with or without 1.5 g/kg EtOH, and were killed at 5, 15 or 60 min after injection. MDMA, its primary metabolite, 3,4-methylenedioxyamphetamine (MDA), and EtOH concentrations were determined in the plasma and the hippocampus, frontal cortex and striatum at each time-point. EtOH potentiated MDMA-induced hyperactivity mainly during the first 60 min post-administration. Fifteen and 60 min after treatment with MDMA and EtOH, MDMA concentrations were greater than after MDMA alone in the blood and the three brain regions examined. EtOH, however, did not increase the fraction of MDMA converted to MDA, as shown by unaltered MDA/MDMA ratios at either MDMA dose. Interestingly, when combined with EtOH, the distribution of MDMA and MDA in the brain was not homogeneous. Concentrations of both were much higher in the striatum and cortex, than in the hippocampus. Thus, at least part of the potentiation of the MDMA-induced hyperlocomotion by EtOH might be the result of a higher concentration of MDMA and metabolites in the blood and brain. Our results present clear evidence that EtOH increases brain and blood concentrations of MDMA and leads to the possibility of both enhanced MDMA-based neurotoxicity and increased liability for abuse.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 13
- Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage Current Pharmaceutical Biotechnology June 27, 2010
- Simultaneous polysubstance use among Danish 3,4‐methylenedioxymethamphetamine and hallucinogen users: combination patterns and proposed biological bases Human Psychopharmacology: Clinical and Experimental June 14, 2012
- Neurotoxicity and persistent cognitive deficits induced by combined MDMA and alcohol exposure in adolescent rats Addiction Biology October 1, 2010
- Adolescent pre‐exposure to ethanol and 3,4‐methylenedioxymethylamphetamine (MDMA) increases conditioned rewarding effects of MDMA and drug‐induced reinstatement Addiction Biology October 13, 2011
- Pills and pints: Risky drinking and alcohol‐related harms among regular ecstasy users in Australia Drug and Alcohol Review September 15, 2011
and 8 more in the library
Cites 9
- Patterns of simultaneous polysubstance use in drug using university students Human Psychopharmacology: Clinical and Experimental June 1, 2006
- Patterns of recreational drug use at dance events in Edinburgh, Scotland Addiction July 1, 2001
- Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers Psychopharmacology February 28, 2008
- Interactions between ethanol and cocaine, amphetamine, or MDMA in the rat: thermoregulatory and locomotor effects. Psychopharmacology March 2008
- Ethanol-MDMA interactions in rats: the importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination. Psychopharmacology July 2007
and 4 more in the library