MDMA ('Ecstasy') enhances 5-HT1A receptor density and 8-OH-DPAT-induced hypothermia: blockade by drugs preventing 5-hydroxytryptamine depletion

Eur J Pharmacol. 1998 Apr 10;346(2-3):181-8. doi: 10.1016/s0014-2999(98)00062-4.

Abstract

One week after a single administration of 3,4-methylenedioxymethamphetamine (MDMA HCI, 30 mg/kg i.p.), 5-HT1A receptor density was significantly increased by approximately 25-30% in the frontal cortex and hypothalamus of rats. The increased density correlated with the potentiation of the hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1 mg/kg s.c.). Hypothalamic 5-HT7 receptors, which also bind 8-OH-DPAT, were not changed, however, by MDMA. Fluoxetine (5 mg/kg s.c.), ketanserin (5 mg/kg s.c.) or haloperidol (2 mg/kg i.p.), given 15 min prior to MDMA, prevented the depletion of 5-hydroxytryptamine (5-HT) induced by MDMA and also blocked the effects of this neurotoxin on 5-HT1A receptor density and on 8-OH-DPAT-induced hypothermia. The protection afforded by drugs against 5-HT loss did not correlate, however, with the antagonism of the acute hyperthermic effect of MDMA. The present results indicate that drugs able to prevent or to attenuate MDMA-induced 5-HT loss also prevent the changes in 5-HT1A receptor density as well as the enhanced hypothermic response to the 5-HT1A receptor agonist 8-OH-DPAT in MDMA-treated rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / antagonists & inhibitors*
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
  • Animals
  • Body Temperature / drug effects
  • Hydroxyindoleacetic Acid / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Hypothermia / chemically induced*
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / antagonists & inhibitors*
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / metabolism*
  • Serotonin Agents / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*
  • Serotonin Uptake Inhibitors / pharmacology*

Substances

  • Receptors, Serotonin
  • Serotonin Agents
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors
  • Hydroxyindoleacetic Acid
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • N-Methyl-3,4-methylenedioxyamphetamine