Interactions between ethanol and cocaine, amphetamine, or MDMA in the rat

Thermoregulatory and locomotor effects

Sami Ben Hamida, Erin Plute, Brigitte Cosquer, Christian Kelche, Byron Jones, Jean Christophe Cassel

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Rationale: (±)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is often taken recreationally with ethanol (EtOH). In rats, EtOH may potentiate MDMA-induced hyperactivity, but attenuate hyperthermia. Objective: Experiment 1 compared the interactions between EtOH (1.5 g/kg) and MDMA (6.6 mg/kg) with EtOH + cocaine (COCA; 10 mg/kg) and EtOH + amphetamine (AMPH; 1 mg/kg) on locomotor activity and thermoregulation. Experiment 2 used a weaker dose of MDMA (3.3 mg/kg) and larger doses of COCA (20 mg/kg) and AMPH (2 mg/kg). Materials and methods: Drug treatments were administered on four occasions (2, 5, and 2 days apart, respectively; experiment 1) or two (2 days apart; experiment 2). Results: All psychostimulants increased activity, and EtOH markedly increased the effect of MDMA. AMPH alone-related hyperactivity showed modest sensitization across treatment days, while MDMA + EtOH activity showed marked sensitization. AMPH, COCA, and MDMA induced hyperthermia of comparable amplitude (+1 to +1.5°C). Co-treatment with EtOH and AMPH (1 mg/kg) or COCA (10 mg/kg) produced hypothermia greater than that produced by EtOH alone. Conversely, EtOH attenuated MDMA-related hyperthermia, an effect increasing across treatment days. These results demonstrate that the interaction between MDMA and EtOH may be different from the interaction between EtOH and AMPH or COCA. Conclusion: Because of potential health-related consequences of such polydrug misuse, it is worth identifying the mechanisms underlying these interactions, especially between EtOH and MDMA. Given the different affinity profiles of the three drugs for serotonin, dopamine, and norepinephrine transporters, our results appear compatible with the possibility of an important role of serotonin in at least the EtOH-induced potentiation of MDMA-induced hyperlocomotion.

Original languageEnglish (US)
Pages (from-to)67-82
Number of pages16
JournalPsychopharmacology
Volume197
Issue number1
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

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N-Methyl-3,4-methylenedioxyamphetamine
Amphetamine
Cocaine
Ethanol
Fever
Norepinephrine Plasma Membrane Transport Proteins
Serotonin Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
Induced Hyperthermia
Body Temperature Regulation
Therapeutics
Locomotion
Hypothermia
Pharmaceutical Preparations
Serotonin

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Interactions between ethanol and cocaine, amphetamine, or MDMA in the rat : Thermoregulatory and locomotor effects. / Hamida, Sami Ben; Plute, Erin; Cosquer, Brigitte; Kelche, Christian; Jones, Byron; Cassel, Jean Christophe.

In: Psychopharmacology, Vol. 197, No. 1, 01.03.2008, p. 67-82.

Research output: Contribution to journalArticle

Hamida, Sami Ben ; Plute, Erin ; Cosquer, Brigitte ; Kelche, Christian ; Jones, Byron ; Cassel, Jean Christophe. / Interactions between ethanol and cocaine, amphetamine, or MDMA in the rat : Thermoregulatory and locomotor effects. In: Psychopharmacology. 2008 ; Vol. 197, No. 1. pp. 67-82.
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abstract = "Rationale: (±)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is often taken recreationally with ethanol (EtOH). In rats, EtOH may potentiate MDMA-induced hyperactivity, but attenuate hyperthermia. Objective: Experiment 1 compared the interactions between EtOH (1.5 g/kg) and MDMA (6.6 mg/kg) with EtOH + cocaine (COCA; 10 mg/kg) and EtOH + amphetamine (AMPH; 1 mg/kg) on locomotor activity and thermoregulation. Experiment 2 used a weaker dose of MDMA (3.3 mg/kg) and larger doses of COCA (20 mg/kg) and AMPH (2 mg/kg). Materials and methods: Drug treatments were administered on four occasions (2, 5, and 2 days apart, respectively; experiment 1) or two (2 days apart; experiment 2). Results: All psychostimulants increased activity, and EtOH markedly increased the effect of MDMA. AMPH alone-related hyperactivity showed modest sensitization across treatment days, while MDMA + EtOH activity showed marked sensitization. AMPH, COCA, and MDMA induced hyperthermia of comparable amplitude (+1 to +1.5°C). Co-treatment with EtOH and AMPH (1 mg/kg) or COCA (10 mg/kg) produced hypothermia greater than that produced by EtOH alone. Conversely, EtOH attenuated MDMA-related hyperthermia, an effect increasing across treatment days. These results demonstrate that the interaction between MDMA and EtOH may be different from the interaction between EtOH and AMPH or COCA. Conclusion: Because of potential health-related consequences of such polydrug misuse, it is worth identifying the mechanisms underlying these interactions, especially between EtOH and MDMA. Given the different affinity profiles of the three drugs for serotonin, dopamine, and norepinephrine transporters, our results appear compatible with the possibility of an important role of serotonin in at least the EtOH-induced potentiation of MDMA-induced hyperlocomotion.",
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