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Repeated exposure to MDMA and amphetamine: sensitization, cross-sensitization, and response to dopamine D1- and D2-like agonists

Abstract

Rationale

Acute exposure to (±) 3, 4-methylenedioxymethamphetamine (MDMA) produces hyperlocomotion that is preferentially expressed in the periphery of closed chambers. Following repeated administration, however, a sensitized hyperlocomotor response is preferentially expressed in the center of an activity box, so that the response resembles the more generalized activity that is produced by d-amphetamine (AMPH).

Objectives

The present study was designed to determine whether common neuroadaptations underlie the acute and sensitized responses to MDMA and AMPH.

Methods

Rats were pretreated with five daily injections of MDMA (10.0 mg/kg), AMPH (2.0 mg/kg), or saline. Following a 2-day drug-free period, dose–response curves for hyperactivity produced by MDMA (2.5–10.0 mg/kg), AMPH (0.5–2.0 mg/kg), SKF-81297 (1.0–2.0 mg/kg), or quinpirole (0.25–1.0 mg/kg) were obtained.

Results

Effects of MDMA and AMPH were increased by pretreatment with both drugs. The sensitized response following MDMA exposure was preferentially expressed in the center compartment, but, following AMPH pretreatment, the sensitized response was observed in both compartments. Cross-sensitization was unidirectional; AMPH pretreatment failed to sensitize to the effects of MDMA, but MDMA pretreatment sensitized to the effects of AMPH. MDMA and AMPH pretreatment produced marginal increases in the effects of SKF-81297. The response to quinpirole was, however, greater following MDMA, but not AMPH, pretreatment.

Conclusions

These data suggest that repeated MDMA exposure produces sensitization via a unique neurochemical effect.

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Royal Society of New Zealand Marsden Fund

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Correspondence to Susan Schenk.

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Bradbury, S., Gittings, D. & Schenk, S. Repeated exposure to MDMA and amphetamine: sensitization, cross-sensitization, and response to dopamine D1- and D2-like agonists. Psychopharmacology 223, 389–399 (2012). https://doi.org/10.1007/s00213-012-2726-9

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Keywords

  • MDMA
  • Amphetamine
  • Sensitization
  • SKF-81297
  • Quinpirole
  • Dopamine
  • Hyperactivity