Ethanol, 3,4-methylenedioxymethamphetamine (ecstasy) and their combination

Long-term behavioral, neurochemical and neuropharmacological effects in the rat

Jean Christophe Cassel, Céline Riegert, Susanne Rutz, Julie Koenig, Katharina Rothmaier, Brigitte Cosquer, Christine Lazarus, Anja Birthelmer, Hélène Jeltsch, Byron Jones, Rolf Jackisch

Research output: Contribution to journalArticle

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Abstract

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 1.5g/kg ethanol and/or 10mg/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.

Original languageEnglish (US)
Pages (from-to)1870-1882
Number of pages13
JournalNeuropsychopharmacology
Volume30
Issue number10
DOIs
StatePublished - Oct 1 2005

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N-Methyl-3,4-methylenedioxyamphetamine
Ethanol
Serotonin
Euthanasia
Injections
Corpus Striatum
Long Evans Rats
Induced Hyperthermia
Hydroxyindoleacetic Acid
Drug Combinations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Ethanol, 3,4-methylenedioxymethamphetamine (ecstasy) and their combination : Long-term behavioral, neurochemical and neuropharmacological effects in the rat. / Cassel, Jean Christophe; Riegert, Céline; Rutz, Susanne; Koenig, Julie; Rothmaier, Katharina; Cosquer, Brigitte; Lazarus, Christine; Birthelmer, Anja; Jeltsch, Hélène; Jones, Byron; Jackisch, Rolf.

In: Neuropsychopharmacology, Vol. 30, No. 10, 01.10.2005, p. 1870-1882.

Research output: Contribution to journalArticle

Cassel, JC, Riegert, C, Rutz, S, Koenig, J, Rothmaier, K, Cosquer, B, Lazarus, C, Birthelmer, A, Jeltsch, H, Jones, B & Jackisch, R 2005, 'Ethanol, 3,4-methylenedioxymethamphetamine (ecstasy) and their combination: Long-term behavioral, neurochemical and neuropharmacological effects in the rat', Neuropsychopharmacology, vol. 30, no. 10, pp. 1870-1882. https://doi.org/10.1038/sj.npp.1300714
Cassel, Jean Christophe ; Riegert, Céline ; Rutz, Susanne ; Koenig, Julie ; Rothmaier, Katharina ; Cosquer, Brigitte ; Lazarus, Christine ; Birthelmer, Anja ; Jeltsch, Hélène ; Jones, Byron ; Jackisch, Rolf. / Ethanol, 3,4-methylenedioxymethamphetamine (ecstasy) and their combination : Long-term behavioral, neurochemical and neuropharmacological effects in the rat. In: Neuropsychopharmacology. 2005 ; Vol. 30, No. 10. pp. 1870-1882.
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