Methylone-induced hyperthermia and lethal toxicity
| Autor: | Yuki Moriya, F. S. Hall, Arihisa Ohara, Klaus-Peter Lesch, Miki Ito, Dennis L. Murphy, Ruri Kikura-Hanajiri, Ichiro Sora, George R. Uhl, Ying Shan Piao, Yukihiro Goda |
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| Přispěvatelé: | Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Fever Methylone Knockout Biology Pharmacology Body Temperature Methamphetamine chemistry.chemical_compound Mice Dopamine receptor D1 Models Internal medicine Dopamine D1 Receptors Dopamine D2 medicine Animals Amphetamine Raclopride Mice Knockout Serotonin Plasma Membrane Transport Proteins SCH-23390 Dopamine Plasma Membrane Transport Proteins Receptors Dopamine D2 Animal Receptors Dopamine D1 Benzazepines Psychiatry and Mental health Endocrinology chemistry Toxicity Models Animal Dopamine Antagonists Central Nervous System Stimulants Female Serotonin medicine.drug |
| Zdroj: | Behavioural Pharmacology, 26(4), 345-52. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 0955-8810 |
| Popis: | Methylone (2-methylamino-1-[3,4-methylenedioxy-phenyl]propan-1-one), an amphetamine analog, has emerged as a popular drug of abuse worldwide. Methylone induces hyperthermia, which is thought to contribute toward the lethal consequences of methylone overdose. Methylone has been assumed to induce hyperthermic effects through inhibition of serotonin and/or dopamine transporters (SERT and DAT, respectively). To examine the roles of each of these proteins in methylone-induced toxic effects, we used SERT and DAT knockout (KO) mice and assessed the hyperthermic and lethal effects caused by a single administration of methylone. Methylone produced higher rates of lethal toxicity compared with other amphetamine analogs in wild-type mice. Compared with wild-type mice, lethality was significantly lower in DAT KO mice, but not in SERT KO mice. By contrast, only a slight diminution in the hyperthermic effects of methylone was observed in DAT KO mice, whereas a slight enhancement of these effects was observed in SERT KO mice. Administration of the selective D1 receptor antagonist SCH 23390 and the D2 receptor antagonist raclopride reduced methylone-induced hyperthermia, but these drugs also had hypothermic effects in saline-treated mice, albeit to a smaller extent than the effects observed in methylone-treated mice. In contradistinction to 3,4-methylenedioxymethamphetamine, which induces its toxicity through SERT and DAT, these data indicate that DAT, but not SERT, is strongly associated with the lethal toxicity produced by methylone, which did not seem to be dependent on the hyperthermic effects of methylone. DAT is therefore a strong candidate molecule for interventions aimed at preventing acute neurotoxic and lethal effects of methylone. |
| Databáze: | OpenAIRE |
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