Ethanol-MDMA interactions in rats: the importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination.
Sami Ben Hamida, Erin Plute, Sonia Bach, Christine Lazarus, Antoine Tracqui, Christian Kelche, Anne Pereira De Vasconcelos, Byron C Jones, Jean-Christophe Cassel
Psychopharmacology July 2007 DOI: 10.1007/s00213-007-0752-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Ethanol MDMA |
| Dose | Ethanol 1.5 g/kg i.p.; MDMA 6.6 mg/kg i.p. |
| Duration | Treatment intervals of 48, 120, and 48 hours; monoamine assessment 2 weeks after treatment; MDMA measurement at 45 minutes post-treatment |
| Topics | MDMA |
| Key findings | Ethanol plus MDMA produced progressive locomotor sensitization and partial protection against hyperthermia that persisted after the first day. Brain monoamine levels were unaffected at two weeks, and ethanol reduced the MDA-to-MDMA ratio by 16% overall and 25% in the striatum, suggesting pharmacokinetic effects. |
Abstract
In our previous work, we showed that ethanol (EtOH) potentiates 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperlocomotion while protecting against its hyperthermic effects. Whereas the effect on activity were found on all days (although declining over the three first days), the protection against hyperthermia completely disappeared on the second day. The latter effect was previously thought to reflect tolerance to ethanol or the combination, per se. In the present study, we changed the treatment regimen to irregular and longer intervals between treatments (48, 120, and again 48 h) to check if tolerance was still observed. We found progressive sensitization of locomotor activity to EtOH (1.5 g/kg, i.p.)+MDMA (6.6 mg/kg, i.p.), and a partial EtOH protection against MDMA-induced hyperthermia that persisted after the first drug challenge day. When the monoamine neurotransmitters, dopamine, and serotonin were assessed 2 weeks after treatment, we found no consistent effect on the concentration of any of these neurotransmitters, whatever the treatment. Similarly, we found that regional brain concentrations of MDMA were not significantly affected by EtOH at a 45-min post-treatment delay; however, the overall ratio of the metabolite 3,4-methylenedioxyamphetamine (MDA) to MDMA was lower (overall, -16%) in animals treated with the combination compared to MDMA alone, indicating possible contribution of pharmacokinetic factors. This difference was especially marked in the striatum (-25%). These findings shed new light on the consequences of EtOH-MDMA, taken together at a nearly normal ambient temperature, both in terms of motivation and potential risks for recreational drug users.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 10
- Ethanol increases the distribution of MDMA to the rat brain: possible implications in the ethanol-induced potentiation of the psychostimulant effects of MDMA The International Journal of Neuropsychopharmacology December 2, 2008
- 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
- Hard Boiled: Alcohol Use as a Risk Factor for MDMA-Induced Hyperthermia: a Systematic Review. Neurotoxicity Research December 2021
- Intermittent ethanol exposure increases long-lasting behavioral and neurochemical effects of MDMA in adolescent mice. Psychopharmacology November 2011
- MDMA: interactions with other psychoactive drugs. Pharmacology, Biochemistry, and Behavior October 2011
and 5 more in the library
Cites 28
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research Human Psychopharmacology: Clinical and Experimental December 1, 2001
- Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Journal of Neuroscience July 1, 1998
- Patterns of simultaneous polysubstance use in drug using university students Human Psychopharmacology: Clinical and Experimental June 1, 2006
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
and 23 more in the library