The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats
Annis O. Mechan, B. Moreno Esteban, Esther O’shea, J.m. Elliott, María Isabel Colado, Alfred Richard Green
British Journal of Pharmacology 2002 DOI: 10.1038/sj.bjp.0704442 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA methysergide MDL 100 907 SB 242084 ritanserin MDL 11 939 zimeldine fluoxetine remoxipride SCH 23390 GBR 12909 |
| Dose | 12.5 mg kg −1 i.p. MDMA, 10 mg kg −1 methysergide, 0.1 mg kg −1 MDL 100,907, 3 mg kg −1 SB 242084, 1 mg kg −1 ritanserin, 5 mg kg −1 MDL 11,939, 10 mg kg −1 zimeldine, 10 mg kg −1 fluoxetine, 10 mg kg −1 remoxipride, 0.3 – 2.0 mg kg −1 SCH 23390, 10 mg kg −1 GBR 12909 |
| Topics | MDMA Serotonin |
| Keywords | Sch-23390 Hyperthermia Pharmacology Ritanserin Microdialysis Methysergide Dopamine antagonist Receptor antagonist |
| Citations | 219 |
| Key findings | MDMA-induced hyperthermia results from increased dopamine release acting at D1 receptors, not from serotonin release. |
Abstract
The pharmacology of the acute hyperthermia that follows 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) administration to rats has been investigated. MDMA (12.5 mg kg −1 i.p.) produced acute hyperthermia (measured rectally). The tail skin temperature did not increase, suggesting that MDMA may impair heat dissipation. Pretreatment with the 5‐HT 1/2 antagonist methysergide (10 mg kg −1 ), the 5‐HT 2A antagonist MDL 100,907 (0.1 mg kg −1 ) or the 5‐HT 2C antagonist SB 242084 (3 mg kg −1 ) failed to alter the hyperthermia. The 5‐HT 2 antagonist ritanserin (1 mg kg −1 ) was without effect, but MDL 11,939 (5 mg kg −1 ) blocked the hyperthermia, possibly because of activity at non‐serotonergic receptors. The 5‐HT uptake inhibitor zimeldine (10 mg kg −1 ) had no effect on MDMA‐induced hyperthermia. The uptake inhibitor fluoxetine (10 mg kg −1 ) markedly attenuated the MDMA‐induced increase in hippocampal extracellular 5‐HT, also without altering hyperthermia. The dopamine D 2 antagonist remoxipride (10 mg kg −1 ) did not alter MDMA‐induced hyperthermia, but the D 1 antagonist SCH 23390 (0.3 – 2.0 mg kg −1 ) dose‐dependently antagonized it. The dopamine uptake inhibitor GBR 12909 (10 mg kg −1 ) did not alter the hyperthermic response and microdialysis demonstrated that it did not inhibit MDMA‐induced striatal dopamine release. These results demonstrate that in vivo MDMA‐induced 5‐HT release is inhibited by 5‐HT uptake inhibitors, but MDMA‐induced dopamine release may not be altered by a dopamine uptake inhibitor. It is suggested that MDMA‐induced hyperthermia results not from MDMA‐induced 5‐HT release, but rather from the increased release of dopamine that acts at D 1 receptors. This has implications for the clinical treatment of MDMA‐induced hyperthermia. British Journal of Pharmacology (2002) 135 , 170–180; doi: 10.1038/sj.bjp.0704442
Comparable studies
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- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- The Norepinephrine Transporter Inhibitor Reboxetine Reduces Stimulant Effects of MDMA (“Ecstasy”) in Humans Clinical Pharmacology & Therapeutics June 15, 2011
- Brain hyperthermia induced by MDMA (‘ecstasy’): modulation by environmental conditions European Journal of Neuroscience July 1, 2004
- Methylenedioxymethamphetamine (MDMA, ‘Ecstasy’): a stressor on the immune system Immunology March 30, 2004
and 65 more in the library
Cites 23
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- In vivo evidence for free radical involvement in the degeneration of rat brain 5‐HT following administration of MDMA (‘ecstasy’) and p‐chloroamphetamine but not the degeneration following fenfluramine British Journal of Pharmacology July 1, 1997
and 18 more in the library