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The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to rats.
Br J Pharmacol 2002; 135(1):170-80BJ

Abstract

1. The pharmacology of the acute hyperthermia that follows 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') administration to rats has been investigated. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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. 8. 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.

Authors+Show Affiliations

Pharmacology Research Group, School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9RH.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11786492

Citation

Mechan, Annis O., et al. "The Pharmacology of the Acute Hyperthermic Response That Follows Administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to Rats." British Journal of Pharmacology, vol. 135, no. 1, 2002, pp. 170-80.
Mechan AO, Esteban B, O'Shea E, et al. The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to rats. Br J Pharmacol. 2002;135(1):170-80.
Mechan, A. O., Esteban, B., O'Shea, E., Elliott, J. M., Colado, M. I., & Green, A. R. (2002). The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to rats. British Journal of Pharmacology, 135(1), pp. 170-80.
Mechan AO, et al. The Pharmacology of the Acute Hyperthermic Response That Follows Administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to Rats. Br J Pharmacol. 2002;135(1):170-80. PubMed PMID: 11786492.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to rats. AU - Mechan,Annis O, AU - Esteban,Blanca, AU - O'Shea,Esther, AU - Elliott,J Martin, AU - Colado,M Isabel, AU - Green,A Richard, PY - 2002/1/12/pubmed PY - 2002/4/27/medline PY - 2002/1/12/entrez SP - 170 EP - 80 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 135 IS - 1 N2 - 1. The pharmacology of the acute hyperthermia that follows 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') administration to rats has been investigated. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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. 8. 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/11786492/The_pharmacology_of_the_acute_hyperthermic_response_that_follows_administration_of_34_methylenedioxymethamphetamine__MDMA_'ecstasy'__to_rats_ L2 - https://doi.org/10.1038/sj.bjp.0704442 DB - PRIME DP - Unbound Medicine ER -