Repeated adolescent MDMA ("Ecstasy") exposure in rats increases behavioral and neuroendocrine responses to a 5-HT2A/2C agonist

Brain Res. 2009 Feb 3:1252:87-93. doi: 10.1016/j.brainres.2008.11.045. Epub 2008 Nov 25.

Abstract

MDMA (3,4-methylenedioxymethamphetamine) is a popular recreational drug among adolescents. The present study aimed to determine the effects of repeated intermittent administration of 10 mg/kg MDMA during adolescence on behavioral (Experiment 1) and neuroendocrine (Experiment 2) responses of rats to the 5-HT(2A/2C) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and on [(3)H]ketanserin binding to 5-HT(2A) receptors. In the first experiment, MDMA pretreatment increased the frequency of head twitches and back muscle contractions, but not wet-dog shakes, to a high-dose DOI challenge. In the second experiment, both the prolactin and corticosterone responses to DOI were potentiated in MDMA-pretreated animals. No changes were found in 5-HT(2A) receptor binding in the hypothalamus or other forebrain areas that were examined. These results indicate that intermittent adolescent MDMA exposure enhances sensitivity of 5-HT(2A/2C) receptors in the CNS, possibly through changes in downstream signaling mechanisms.

MeSH terms

  • Amphetamines / pharmacology*
  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Brain / metabolism
  • Corticosterone / blood
  • Ketanserin / metabolism
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage*
  • Neurosecretory Systems / drug effects*
  • Prolactin / blood
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Serotonin 5-HT2 Receptor Agonists*
  • Serotonin Agents / pharmacology

Substances

  • Amphetamines
  • Receptor, Serotonin, 5-HT2A
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin Agents
  • Prolactin
  • Ketanserin
  • N-Methyl-3,4-methylenedioxyamphetamine
  • 4-iodo-2,5-dimethoxyphenylisopropylamine
  • Corticosterone