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

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.