Ethanol, 3,4-Methylenedioxymethamphetamine (Ecstasy) and Their Combination: Long-Term Behavioral, Neurochemical and Neuropharmacological Effects in the Rat

Abstract

This study investigated long-term behavioral, neurochemical, and neuropharmacological effects of ethanol-(7)-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 longterm, 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 methiotepininduced 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.

A developmental comparison of the neurobehavioral effects of ecstasy (MDMA)

“…Recent investigations have begun to determine that humans may exhibit similar alterations in 5-HT and serotonergic mediated function due to repeated ecstasy use [61,66,72,113]. As ecstasy is typically used recreationally with other substances, researchers have begun to determine how MDMA interacts with alcohol [21], caffeine [95], LSD [137], marijuana [107] and methamphetamine [24][25][26] in adults.…”

Relevance of rodent models of intravenous MDMA self-administration to human MDMA consumption patterns

“…Marijuana exposure likely contributes to a number of prevalent psychobiological symptoms, including psychosis, reported by MDMA users (Milani et al 2005;Parrott 2004Parrott , 2005. For alcohol, a recent preclinical report revealed that MDMA-ethanol interactions may have specific long-term consequences on presynaptic modulation of hippocampal 5-HT release, which is not necessarily related to MDMA-induced depletion of 5-HT (Cassel et al 2005). The authors speculated that the psychopathological problems reported by ecstasy users drinking alcohol are unlikely to be the sole result of the consumption of MDMA.…”

Amnésie antérograde consécutive à l’absorption de MDMA et d’alcool : à propos d’un cas

“…Certains effets de l'association MDMA/ éthanol, au niveau de l'hippocampe, avaient été mis en évidence auparavant chez l'animal. Cassel et al [23] ont en effet démontré qu'une telle combinaison pouvait avoir des conséquences spécifiques à long terme sur la modulation de la libération de sérotonine au niveau de l'hippocampe, indépendamment de la neurotoxicité propre de la MDMA.…”