The N-methyl-D-aspartate antagonist MK-801 protects against serotonin depletions induced by methamphetamine, 3,4-methylenedioxymethamphetamine and p-chloroamphetamine.
G M Farfel, Georgetta Vosmer, Lewis S. Seiden
Brain Research November 1, 1992 DOI: 10.1016/0006-8993(92)91460-v (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Male rats |
| Interventions | MK-801 D-methamphetamine 3 4-Methylenedioxymethamphetamine (MDMA) p-Chloroamphetamine (PCA) |
| Dose | MK-801 0.5, 1.0 or 2.5 mg/kg; MA 10.0, 20.0 or 40.0 mg/kg given as 4, 2 or 1 injection(s); MDMA 20.0 or 40.0 mg/kg; PCA 5.0 or 10.0 mg/kg |
| Duration | 72 hours after the last injection |
| Topics | Serotonin MDMA |
| Keywords | Hippocampus Corpus striatum Animals Rats P-chloroamphetamine Methamphetamine N-methyl-3,4-methylenedioxyamphetamine Dizocilpine maleate N-methylaspartate |
| Key findings | MK-801 attenuated serotonin depletion caused by methamphetamine, MDMA, and p-chloroamphetamine in rat hippocampus and striatum. Methamphetamine (4 x 10.0 mg/kg) depleted serotonin to 33% of control in hippocampus and 50% in striatum; co-administered MK-801 (2.5 mg/kg) kept serotonin at control levels in both regions. MDMA at 40 mg/kg depleted serotonin to roughly 58% (hippocampus) and 66% (striatum) of control. |
Abstract
The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocks the ability of D-methamphetamine (MA) to deplete striatal dopamine (DA). We now report that MK-801 attenuates decreases in serotonin (5-HT) concentration induced by MA and two other amphetamine analogues, 3,4-methylenedioxymethamphetamine (MDMA) and p-chloroamphetamine (PCA). Rats were injected with saline (1.0 ml/kg) or MK-801 (0.5, 1.0 or 2.5 mg/kg) followed by either saline (1.0 mg/kg), MA (4, 2 or 1 injection(s); 10.0, 20.0 or 40.0 mg/kg), MDMA (20.0 or 40.0 mg/kg) or PCA (5.0 or 10.0 mg/kg). In some experiments, two injections of MK-801 or saline were used. Seventy-two hours after the last injection rats were sacrificed and concentrations of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and DA were determined in hippocampus and striatum. MA caused a depletion of 5-HT to 33% of control in hippocampus and to 50% of control in striatum after the 4 x 10.0 mg/kg dose regimen. When MK-801 (2.5 mg/kg) was co-administered with MA, concentrations of 5-HT did not differ from control levels in either brain region. MDMA depleted 5-HT to approximately 58% of control in hippocampus and 66% of control in striatum at the 40 mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- 3,4-methylenedioxymethamphetamine (‘Ecstasy’) promotes the translocation of protein kinase C (PKC): requirement of viable serotonin nerve terminals Brain Research May 1, 1995
- Dextromethorphan moderates reward deficiency associated with central serotonin transporter availability in 3,4-methylenedioxy-methamphetamine-treated animals. Journal of the Chinese Medical Association : JCMA May 1, 2024
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Cites 10
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- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography Synapse August 1, 1991
- Antagonism of the neurotoxicity due to a single administration of methylenedioxymethamphetamine. European Journal of Pharmacology May 31, 1990
- 5-HT2 antagonists stereoselectively prevent the neurotoxicity of 3,4-methylenedioxymethamphetamine by blocking the acute stimulation of dopamine synthesis: reversal by L-dopa. Journal of Pharmacology and Experimental Therapeutics 1990
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