Effects of repeated exposure to MDMA on 5HT1a autoreceptor function: behavioral and neurochemical responses to 8-OHDPAT

Psychopharmacology (Berl). 2013 May;227(2):355-61. doi: 10.1007/s00213-013-2980-5. Epub 2013 Jan 25.


A consistent effect of repeated exposure to 3,4 methylenedioxymethamphetamine (MDMA) is a decrease in the tissue levels of serotonin (5-HT). A variety of behavioural and neurochemical tests were conducted to determine whether the tissue deficits were accompanied by an increased sensitivity of the 5-HT1a autoreceptor. Tests were conducted 2 weeks following MDMA exposure (four injections of 10.0 mg/kg, IP, administered at 2-h intervals in a single day). The response to the 5-HT1a agonist, 8-OHDPAT (0.003-0.5 mg/kg, SC), was assessed using lower lip retraction (LLR), hypoactivity, and 5-hydroxytryptophan (5-HTP) accumulation following decarboxylase inhibition. The 8-OHDPAT produced a dose-dependent increase in LLR and hypoactivity, but these effects were comparable for MDMA and saline pretreated groups. MDMA decreased tissue levels of 5-HT and the accumulation of 5-HTP, but these effects were not reflected in the changes in autoreceptor sensitivity. The data suggest that the decrease in tissue levels of 5-HT produced by MDMA is accompanied by a decrease in tryptophan hydroxylase activity but cannot be explained by supersensitivity of the 5-HT1a autoreceptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Hydroxytryptophan / metabolism
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / administration & dosage
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
  • Animals
  • Autoreceptors / drug effects
  • Autoreceptors / metabolism
  • Behavior, Animal / drug effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Serotonin / metabolism
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology*
  • Tryptophan Hydroxylase / metabolism


  • Autoreceptors
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • 5-Hydroxytryptophan
  • Tryptophan Hydroxylase
  • N-Methyl-3,4-methylenedioxyamphetamine