MDMA ("ecstacy"), methamphetamine and their combination: long-term changes in social interaction and neurochemistry in the rat

Kelly J. Clemens, Petra Van Nieuwenhuyzen, Kong M. Li, Jennifer L. Cornish, Glenn Hunt, Iain Mcgregor

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

Abstract

Rationale: 3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) are illicit drugs that are increasingly used in combination. The acute and long-term effects of MDMA/METH combinations are largely uncharacterised. Objectives: The current study investigated the behavioural, thermal and neurotoxic effects of MDMA and METH when given alone or in combined low doses. Methods: Male rats received four injections, one every 2 h, of vehicle, MDMA (2.5 or 5 mg/ kg per injection), METH (2.5 or 5 mg/kg per injection) or combined MDMA/METH (1.25+1.25 mg/kg per injection or 2+2 mg/kg per injection). Drugs were given at an ambient temperature of 28°C to simulate hot nightclub conditions. Body temperature, locomotor activity and head-weaving were assessed during acute drug administration while social interaction, anxiety-related behavior on the emergence test and neurochemical parameters were assessed 4-7 weeks later. Results: All treatments acutely increased locomotor activity, while pronounced head-weaving was seen with both MDMA/METH treatments and the higher dose METH treatment. Acute hyperthermia was greatest with the higher dose MDMA/ METH treatment and was also seen with MDMA but not METH treatment. Several weeks after drug administration, both MDMA/METH groups, both METH groups and the higher dose MDMA group showed decreased social interaction relative to controls, while both MDMA/ METH groups and the lower dose MDMA group showed increased anxiety-like behaviour on the emergence test. MDMA treatment caused 5-HT and 5-HIAA depletion in several brain regions, while METH treatment reduced dopamine in the prefrontal cortex. Combined MDMA/ METH treatment caused 5-HT and 5-HIAA depletion in several brain regions and a unique depletion of dopamine and DOPAC in the striatum. Conclusions: These results suggest that MDMA and METH in combination may have greater adverse acute effects (head-weaving, body temperature) and long-term effects (decreased social interaction, increased emergence anxiety, dopamine depletion) than equivalent doses of either drug alone.

Original languageEnglish
Pages (from-to)318-325
Number of pages8
JournalPsychopharmacology
Volume173
Issue number3-4
DOIs
Publication statusPublished - May 2004
Externally publishedYes

Keywords

  • 5-HT
  • Anxiety
  • Dopamine
  • Ecstasy
  • MDMA
  • Methamphetamine
  • Polydrug use

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