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Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity in rat brain.
Psychopharmacology (Berl). 2007 Jan; 189(4):459-70.P

Abstract

RATIONALE

Ecstasy abuse commonly occurs in hot, overcrowded environments in combination with alcohol. Around 90% of ecstasy users take ethanol; over 70% of these users also often drink alcohol at hazardous levels.

OBJECTIVES

We wished to examine whether binge ethanol administration enhanced the long-lasting 5-HT neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats maintained at high ambient temperature and the role of acetaldehyde.

MATERIALS AND METHODS

Rats were treated with a 4-day ethanol regimen leading to plasma ethanol levels of around 450 mg/dl. On day 5, rats were placed at 30 degrees C and administered MDMA (5 mg/kg). Rectal temperature and hydroxyl radical formation were measured immediately before and up to 6 h after MDMA. 5-HT concentration and 5-HT transporter density were determined 7 days later. A group of rats received cyanamide (50 mg/kg) on days 1 and 3 of the 4-day-ethanol inhalation.

RESULTS

In ethanol treated rats, MDMA produced a hyperthermic response similar to that observed in controls but enhanced the loss of 5-HT concentration and 5-HT transporter density in the hippocampus. Cyanamide elevated the plasma acetaldehyde concentration fivefold to sevenfold, reduced the MDMA-induced hyperthermia and increased the neuronal damage with neurotoxicity also appearing in the cortex. MDMA increased hydroxyl radical production in the hippocampus, the effect being more marked in rats pre-exposed to ethanol.

CONCLUSIONS

Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity by a mechanism not related to changes in acute hyperthermia but probably involving hydroxyl radical formation. The magnitude of this effect is more pronounced after increasing plasma acetaldehyde levels by aldehyde dehydrogenase inhibition.

Authors+Show Affiliations

Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, 28040, Spain.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17047928

Citation

Izco, María, et al. "Binge Ethanol Administration Enhances the MDMA-induced Long-term 5-HT Neurotoxicity in Rat Brain." Psychopharmacology, vol. 189, no. 4, 2007, pp. 459-70.
Izco M, Orio L, O'Shea E, et al. Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity in rat brain. Psychopharmacology (Berl). 2007;189(4):459-70.
Izco, M., Orio, L., O'Shea, E., & Colado, M. I. (2007). Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity in rat brain. Psychopharmacology, 189(4), 459-70.
Izco M, et al. Binge Ethanol Administration Enhances the MDMA-induced Long-term 5-HT Neurotoxicity in Rat Brain. Psychopharmacology (Berl). 2007;189(4):459-70. PubMed PMID: 17047928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity in rat brain. AU - Izco,María, AU - Orio,Laura, AU - O'Shea,Esther, AU - Colado,M Isabel, Y1 - 2006/10/18/ PY - 2006/06/16/received PY - 2006/09/26/accepted PY - 2006/10/19/pubmed PY - 2007/3/3/medline PY - 2006/10/19/entrez SP - 459 EP - 70 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 189 IS - 4 N2 - RATIONALE: Ecstasy abuse commonly occurs in hot, overcrowded environments in combination with alcohol. Around 90% of ecstasy users take ethanol; over 70% of these users also often drink alcohol at hazardous levels. OBJECTIVES: We wished to examine whether binge ethanol administration enhanced the long-lasting 5-HT neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats maintained at high ambient temperature and the role of acetaldehyde. MATERIALS AND METHODS: Rats were treated with a 4-day ethanol regimen leading to plasma ethanol levels of around 450 mg/dl. On day 5, rats were placed at 30 degrees C and administered MDMA (5 mg/kg). Rectal temperature and hydroxyl radical formation were measured immediately before and up to 6 h after MDMA. 5-HT concentration and 5-HT transporter density were determined 7 days later. A group of rats received cyanamide (50 mg/kg) on days 1 and 3 of the 4-day-ethanol inhalation. RESULTS: In ethanol treated rats, MDMA produced a hyperthermic response similar to that observed in controls but enhanced the loss of 5-HT concentration and 5-HT transporter density in the hippocampus. Cyanamide elevated the plasma acetaldehyde concentration fivefold to sevenfold, reduced the MDMA-induced hyperthermia and increased the neuronal damage with neurotoxicity also appearing in the cortex. MDMA increased hydroxyl radical production in the hippocampus, the effect being more marked in rats pre-exposed to ethanol. CONCLUSIONS: Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity by a mechanism not related to changes in acute hyperthermia but probably involving hydroxyl radical formation. The magnitude of this effect is more pronounced after increasing plasma acetaldehyde levels by aldehyde dehydrogenase inhibition. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/17047928/Binge_ethanol_administration_enhances_the_MDMA_induced_long_term_5_HT_neurotoxicity_in_rat_brain_ L2 - https://dx.doi.org/10.1007/s00213-006-0602-1 DB - PRIME DP - Unbound Medicine ER -