Preexposure to MDMA ("Ecstasy") delays acquisition but facilitates MDMA-induced reinstatement of amphetamine self-administration behavior in rats

Kirsten C. Morley, Jennifer L. Cornish, Kong M. Li, Iain S. McGregor

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

The current experiment investigated the effect of 3,4- methylenedioxymethamphetamine (MDMA; 'Ecstasy') preexposure on the acquisition of intravenous amphetamine self-administration and the reinstatement of amphetamine-seeking behavior by either MDMA or amphetamine. Rats were preexposed to a 5-HT depleting regime of MDMA (5 mg/kg every hour for 4 h on two consecutive days) or equivalent vehicle injections. Intravenous self-administration of low dose d-amphetamine (0.03 mg/kg/infusion) on a FR1 schedule was subsequently assessed. The rats were then given 2 weeks of extinction and tested for drug-seeking behavior with priming doses of amphetamine or MDMA. Brains were analysed for monoamine content using high-performance liquid chromatography (HPLC). MDMA-preexposed rats were initially slower to acquire amphetamine self-administration. However, by day 6 of acquisition, there was no difference from controls. Following extinction, amphetamine (1 mg/kg, i.p.) reinstated drug seeking and produced locomotor hyperactivity in both MDMA- and vehicle-pretreated animals. However, MDMA (5 mg/kg, i.p.) was only effective in producing amphetamine seeking and hyperactivity in MDMA-pretreated rats. MDMA pretreatment caused significant decreases in 5-hydroxy-indolacetic acid (5-HIAA) and 5-HT in several brain regions. These results suggest that 5-HT depletion induced by MDMA may initially slow the acquisition of amphetamine self-administration but that MDMA preexposure may also sensitize animals to the locomotor stimulating and priming effects of MDMA on drug-seeking behavior.

Original languageEnglish
Pages (from-to)331-342
Number of pages12
JournalPharmacology Biochemistry and Behavior
Volume79
Issue number2
DOIs
Publication statusPublished - Oct 2004
Externally publishedYes

Keywords

  • Acquisition
  • Amphetamine
  • Ecstasy
  • Extinction
  • Maintenance
  • MDMA
  • Neurotoxicity
  • Reinstatement
  • Self-administration
  • Serotonin

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