The effect of (R)-HA966 or ACEA 1021 on dexfenfluramine or (S)-MDMA-induced changes in temperature, activity, and neurotoxicity

Pharmacol Biochem Behav. 2001 Mar;68(3):565-74. doi: 10.1016/s0091-3057(01)00454-3.

Abstract

The glycine site-specific N-methyl-D-aspartate (NMDA) antagonist 5-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021, 4x30 mg/kg, i.p.) given 30 min before dexfenfluramine (4x15 mg/kg, i.p., every 2 h) was unable to prevent dexfenfluramine-induced depletion of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) content, and 5-HT transporter (5-HTT) density. Another glycine site-specific NMDA antagonist, R(+)-3-aminohydroxypyrrolidin-2-one [(R)-HA 966] (2x30 mg/kg, ip), given 30 min before dexfenfluramine (2x10 mg/kg, ip, 2 hourly) was also unable to prevent regional depletion of 5-HT, 5-HIAA, and 5-HTT density. However, ACEA 1021 (4x30 mg/kg, i.p.) given 30 min before (S)-3,4-methylenedioxymethamphetamine (MDMA, 4x10 mg/kg, 2 hourly, ip) attenuated the regional depletion of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 5-HT, 5-HIAA content, and 5-HTT density. ACEA 1021 combined with (S)-MDMA also prevented (S)-MDMA-induced hyperthermia without causing hypothermia or preventing an (S)-MDMA-induced increase in locomotor activity.

MeSH terms

  • Animals
  • Autoradiography
  • Body Temperature / drug effects*
  • Brain Chemistry / drug effects
  • Carrier Proteins / metabolism
  • Chromatography, High Pressure Liquid
  • Dexfenfluramine / pharmacology*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Male
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Motor Activity / drug effects*
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Nerve Tissue Proteins*
  • Neurotoxicity Syndromes / psychology*
  • Pyrrolidinones / pharmacology*
  • Quinoxalines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Receptor Agonists / pharmacology*
  • Stereoisomerism
  • Telemetry

Substances

  • Carrier Proteins
  • Excitatory Amino Acid Antagonists
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Pyrrolidinones
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Receptor Agonists
  • Slc6a4 protein, rat
  • Serotonin
  • licostinel
  • Dexfenfluramine
  • 1-hydroxy-3-amino-2-pyrrolidone
  • N-Methyl-3,4-methylenedioxyamphetamine