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 Jones, Jean Christophe Cassel

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Rationale: 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. Objective: 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. Results: 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%). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)555-569
Number of pages15
JournalPsychopharmacology
Volume192
Issue number4
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

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N-Methyl-3,4-methylenedioxyamphetamine
Ethanol
Therapeutics
Neurotransmitter Agents
3,4-Methylenedioxyamphetamine
Induced Hyperthermia
Street Drugs
Locomotion
Drug Users
Dopamine
Serotonin
Fever
Pharmacokinetics
Temperature
Brain
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Ethanol-MDMA interactions in rats : The importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination. / Ben Hamida, Sami; Plute, Erin; Bach, Sonia; Lazarus, Christine; Tracqui, Antoine; Kelche, Christian; De Vasconcelos, Anne Pereira; Jones, Byron; Cassel, Jean Christophe.

In: Psychopharmacology, Vol. 192, No. 4, 01.07.2007, p. 555-569.

Research output: Contribution to journalArticle

Ben Hamida, Sami ; Plute, Erin ; Bach, Sonia ; Lazarus, Christine ; Tracqui, Antoine ; Kelche, Christian ; De Vasconcelos, Anne Pereira ; Jones, Byron ; Cassel, Jean Christophe. / Ethanol-MDMA interactions in rats : The importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination. In: Psychopharmacology. 2007 ; Vol. 192, No. 4. pp. 555-569.
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