Ethanol-MDMA interactions in rats: the importance of interval between repeated treatments in biobehavioral tolerance and sensitization to the combination.
BACKGROUND
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.
Ben Hamida
Sami
S
LINC-UMR 7191, Université Louis Pasteur-CNRS, Institut Fédérératif de Recherche 37, GDR CNRS 2905, Strasbourg, France.
Plute
Erin
E
Bach
Sonia
S
Lazarus
Christine
C
Tracqui
Antoine
A
Kelche
Christian
C
de Vasconcelos
Anne Pereira
AP
Jones
Byron C
BC
Cassel
Jean-Christophe
JC
D015104:3,4-Methylenedioxyamphetamine / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004347:Drug Interactions; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans
D015306:Biogenic Monoamines; D002492:Central Nervous System Depressants; D006213:Hallucinogens; D000431:Ethanol; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine