Ethanol, 3,4-methylenedioxymethamphetamine (ecstasy) and their combination: long-term behavioral, neurochemical and neuropharmacological effects in the rat.
This study investigated long-term behavioral, neurochemical, and neuropharmacological effects of ethanol-(+/-)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) combinations. Over 4 consecutive days, male Long-Evans rats received 1.5 g/kg ethanol and/or 10 mg/kg MDMA, or saline. Rectal temperatures were taken in some rats. Starting 4 days after the last injection, we tested working memory, sensory-motor coordination, and anxiety. Subsequently, we measured cortical, striatal, septal, and hippocampal monoamines (last MDMA injection-euthanasia delay: 20 days), or electrically evoked release of serotonin (5-HT) in cortical and hippocampal slices, and its modulation in the presence of CP 93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrollo[3,2-b]pyrid-5-one) or methiotepin (last MDMA injection-euthanasia delays: 3-6 weeks). Ethanol attenuated the MDMA-induced hyperthermia, but only on the first day. In the long-term, MDMA reduced 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content in most brain regions. The behavioral and neurochemical effects of the ethanol-MDMA combination were comparable to those of MDMA alone; sensory-motor coordination was altered after ethanol and/or MDMA. In hippocampal slices from rats given ethanol and MDMA, the CP 93,129-induced inhibition and methiotepin-induced facilitation of 5-HT release were stronger and weaker, respectively, than in the other groups. This is the first study addressing long-term effects of repeated MDMA and EtOH combined treatments in experimental animals. Whereas the drug combination produced the same behavioral and neurochemical effects as MDMA alone, our neuropharmacological results suggest that MDMA-EtOH interactions may have specific long-term consequences on presynaptic modulation of hippocampal 5-HT release, but not necessarily related to MDMA-induced depletion of 5-HT. Thus, it is likely that the psycho(patho)logical problems reported by ecstasy users drinking alcohol are not solely due to the consumption of MDMA.
Cassel
Jean-Christophe
JC
Laboratoire de Neurosciences Comportementales et Cognitives, UMR 7521, CNRS/Université Louis Pasteur, GDR 2905 CNRS, IFR 37 Neurosciences, 12 rue Goethe, F-67000 Strasbourg, France. jean-christophe.cassel@psycho-ulp.u-strasbg.fr
Riegert
Céline
C
Rutz
Susanne
S
Koenig
Julie
J
Rothmaier
Katharina
K
Cosquer
Brigitte
B
Lazarus
Christine
C
Birthelmer
Anja
A
Jeltsch
Hélène
H
Jones
Byron C
BC
Jackisch
Rolf
R
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004338:Drug Combinations; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D015306:Biogenic Monoamines; D002492:Central Nervous System Depressants; D004338:Drug Combinations; D006213:Hallucinogens; D012701:Serotonin; D000431:Ethanol; D018817:N-Methyl-3,4-methylenedioxyamphetamine