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.