Ethanol increases the distribution of MDMA to the rat brain: possible implications in the ethanol-induced potentiation of the psychostimulant effects of MDMA.
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.
Hamida
Sami Ben
SB
LINC UMR 7191, CNRS-Université Louis Pasteur, Institut Fédérératif de Recherche 37, Strasbourg, France.
Tracqui
Antoine
A
de Vasconcelos
Anne Pereira
AP
Szwarc
Esther
E
Lazarus
Christine
C
Kelche
Christian
C
Jones
Byron C
BC
Cassel
Jean-Christophe
JC
D015104:3,4-Methylenedioxyamphetamine / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006213:Hallucinogens / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
D002492:Central Nervous System Depressants; D006213:Hallucinogens; D000431:Ethanol; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine