The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to rats
The pharmacology of the acute hyperthermic response that follows administration of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') to rats
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DOI：
10.1038/sj.bjp.0704442
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发表时间：
2002-01-01
影响因子：
7.3
通讯作者：
Green, AR
中科院分区：
文献类型：
--
作者：
Mechan, AO;Esteban, B;Green, AR
1 3.4-亚甲二氧基甲基苯丙胺（MDMA）后急性高热的药理学。2 MDMA（12.5 mg/kg（1）i.p.）产生急性高热（直肠测量）。尾部皮肤温度没有增加。提示MDMA可能损害热耗散。3用5-HT 12拮抗剂异麦角新碱（10 mg kg（-1））、5-HT 2A拮抗剂MDL 100.907（0.1 mg kg（-1））或5-HT 2C拮抗剂SB 242084（3 mg kg（-1））预处理未能改变高热。5-HT 2拮抗剂利坦色林（1 mg kg（1））没有作用，但MDL 11，939（5 mg kg（-1））阻断了体温过高，可能是因为对非肾上腺素能受体的活性。4 5-HT摄取抑制剂zimeldine（10 mg kg（1））对MDMA诱导的体温过高没有作用。摄取抑制剂氟西汀（10 mg kg（1））显著减弱了MDMA诱导的海马细胞外5-HT的增加，也没有改变高血压。5多巴胺D-2拮抗剂瑞莫西必利（10 mg/kg）没有改变MDMA诱导的体温过高，但D-1拮抗剂SCH 23390（0.3-2.0 mg kg（-1））剂量依赖性拮抗它。6多巴胺摄取抑制剂GBR 12909（10 mg kg（1））没有改变高热反应，微透析证明它没有抑制MDMA诱导的纹状体多巴胺释放。7这些结果表明，体内MDMA诱导的5-HT释放被5-HT摄取抑制剂抑制，但MDMA诱导的多巴胺释放可能不会被多巴胺摄取通道改变。8这表明MDMA诱导的体温过高不是由MDMA诱导的5-HT释放引起的。而是由于作用于D1受体的多巴胺释放增加。这对MDMA诱导的高热的临床治疗具有意义。
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-HT1 2 antagonist imethysergide (10 mg kg(-1)), the 5-HT2A antagonist MDL 100.907 (0.1 mg kg(-1)) or the 5-HT2C antagonist SB 242084 (3 mg kg (1)) failed to alter the hyperthermia. The 5-HT2, 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-serotoriergic receptors.4 The 5-HT uptake inhibitor zimeldine (10 mg kg (1)) had no effect oil 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, receptors. This has implications for the clinical treatment of MDMA-induced hyperthermia.