title: Administration of rotenone enhanced voluntary alcohol drinking behavior in C57BL/6J mice.
abstract: Rotenone, a commonly used lipophic pesticide, is a high-affinity mitochondrial complex I inhibitor. The aim of this project is to study the causal relationship between changes of brain monoamine levels and drinking behavior in rotenone-treated mice. In the first experiment, we investigated the effects of acute exposure to rotenone (20 mg/kg, p.o.) on the 8-h time limited-access alcohol drinking behavior and brain monoamine levels in C57BL/6J mice at 0, 2, 8 and 24 h. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5HIAA) levels in the nucleus accumbens (ACC), caudate-putamen (C/P) and lateral hypothalamus (LH) of rotenone-treated mice were decreased at 2 and/or 8 h. Rotenone-exposed mice showed a suppression of voluntary alcohol intake at 4 and 8 h, but total daily alcohol intake did not differ significantly between the two groups. The effects of chronic exposure to rotenone (1, 5, 10 and 20 mg/kg, p.o. for 30 days) on the alcohol drinking behavior and monoamine levels of rotenone-exposed mice (10 mg/kg, p.o.) were investigated in the second experiment. The mice treated with rotenone showed increases in alcohol drinking behavior. Levels of DA and 5-HT in the ACC and C/P of chronic rotenone-treated mice were decreased, while the ratios of DOPAC to DA in the ACC and C/P and of 5HIAA to 5-HT in the ACC, C/P and DRN were increased significantly. Tyrosine hydroxylase immunoreactivity of chronic rotenone-treated mice (10 mg/kg, p.o.) slightly were decreased in both the striatum and the substantia nigra. Ethanol and acetaldehyde metabolism was not significantly different between mice treated with rotenone (10 mg/kg, p.o.) and controls. It was suggested that rotenone-treated mice had increased alcohol drinking behavior associated with increases in the DA turnover ratios of ACC and striatum to compensate for the neural degeneration.
authors.affiliation: Department of Forensic Medicine, Kyoto Prefectural University of Medicine, Kawaramachi, Kamigyo-ku, Kyoto 602-8566, Japan. kyoshimo@koto.kpu-m.ac.jp
authors.forename: Kanji
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ueda
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inden
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hattori
authors.forename: Noboru
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Stuart
authors.initials: S
authors.lastname: McLean
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegaya
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D007306:Insecticides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012402:Rotenone / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D015306:Biogenic Monoamines; D007306:Insecticides; D012402:Rotenone; D004298:Dopamine