Effects of fenfluramine, m-CPP and triazolam on repeated-acquisition in squirrel monkeys before and after neurotoxic MDMA administration

Peter J. Winsauer, Una D. McCann, J. Yuan, Marcus S. Delatte, Michael W. Stevenson, George A. Ricaurte, Joseph M. Moerschbaecher

Research output: Contribution to journalArticle

Abstract

Rationale: Establishing functional deficits as a result of neurotoxic dosing regimens of MDMA has been difficult. However, moderate success has been achieved when sensitive animal models and drug challenge have been used together. Objective: The present study used a repeated-acquisition technique and dose-effect determinations before, during and after neurotoxic MDMA exposure to characterize the effects of serotonergic drugs on learning, and to determine if MDMA-induced serotonin (5-HT) neurotoxicity is associated with learning deficits as measured by changes in response rate or the percentage of errors. Method: The effects of various serotonergic drugs were characterized in six squirrel monkeys responding under a repeated-acquisition procedure before and after neurotoxic dose regimens of MDMA. Specifically, cumulative dose-effect curves for m-CPP (0.032-1 mg/kg), fenfluramine (0.1-3.2 mg/kg) and triazolam (0.0032-0.1 mg/kg) were obtained prior to MDMA administration, with the latter drug serving as a non-5-HT control. Results: In general, all of the drugs tested decreased overall response rate as the cumulative dose increased, whereas only triazolam markedly increased the percentage of errors. MDMA treatment produced significant (80-99%) decreases in brain 5-HT and 5-HIAA axonal markers, but did not lead to changes in either dependent measure of responding or shifts in the dose-effect curves obtained during pharmacological challenges with m-CPP, fenfluramine or triazolam. Conclusions: Taken together, these results demonstrate that serotonergic drugs can disrupt learning in monkeys, but indicate that MDMA-induced 5-HT neurotoxicity does not lead to disruptions in this particular type of serial learning task.

Original languageEnglish (US)
Pages (from-to)388-396
Number of pages9
JournalPsychopharmacology
Volume159
Issue number4
DOIs
StatePublished - Feb 23 2002

Keywords

  • Fenfluramine
  • MDMA
  • Repeated acquisition
  • Squirrel monkey
  • Triazolam
  • m-CPP

ASJC Scopus subject areas

  • Pharmacology

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