Melatonin in concentrated ethanol and ethanol alone attenuate methamphetamine-induced dopamine depletions in C57BL/6J mice.
The present study aimed to investigate the protective effects of melatonin, ethanol and temperature changes on methamphetamine-induced neurotoxicity in both sexes of mice. Mice exhibited a similar degree of striatal dopamine depletion when methamphetamine was administered during the light and dark cycles. Moreover, 10 mg/kg, but not 5 mg/kg, of methamphetamine, significantly increased body temperature even though dopamine depletions were observed following both doses. Melatonin (80 mg/kg) dissolved in 30% (v/v) ethanol and 30% ethanol alone exerted a moderate to full protection against methamphetamine-induced dopamine depletions in both sexes of mice, whereas the same dose of melatonin in 3% ethanol exerted no protective effect. Furthermore, ethanol attenuated methamphetamine-induced dopamine depletions in a dose-dependent manner with the exception of high efficacy of ethanol at low doses. Finally, the protective effects of ethanol were not blocked by bicuculline. Together, we conclude that ethanol may protect mice against methamphetamine-induced dopamine depletion probably via non-GABAA receptor activation.
Yu
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Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, 1 University Road, Tainan 70101, Taiwan. lungyu@mail.ncku.edu.tw
Cherng
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Chen
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000502:physiology; D003624:Darkness; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D008029:Lighting; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008694:Methamphetamine; D051379:Mice; D008810:Mice, Inbred C57BL
D000975:Antioxidants; D002492:Central Nervous System Depressants; D015259:Dopamine Agents; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D000431:Ethanol; D008694:Methamphetamine; D008550:Melatonin; D004298:Dopamine; D001640:Bicuculline