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

Psychopharmacology (Berl). 2002 Feb;159(4):388-96. doi: 10.1007/s00213-001-0942-9. Epub 2001 Nov 23.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • Fenfluramine / pharmacology*
  • GABA Modulators / pharmacology
  • Hydroxyindoleacetic Acid / metabolism
  • Learning / drug effects
  • Learning / physiology
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
  • Piperazines / pharmacology*
  • Reaction Time / drug effects*
  • Reaction Time / physiology
  • Saimiri
  • Serotonin / metabolism
  • Serotonin Agents / toxicity*
  • Serotonin Receptor Agonists / pharmacology
  • Triazolam / pharmacology*


  • GABA Modulators
  • Piperazines
  • Serotonin Agents
  • Serotonin Receptor Agonists
  • Triazolam
  • Fenfluramine
  • Serotonin
  • Hydroxyindoleacetic Acid
  • N-Methyl-3,4-methylenedioxyamphetamine
  • 1-(3-chlorophenyl)piperazine