Citation

Yoshimoto K, Ueda S, Kitamura Y, Inden M, Hattori H, Ishikawa N, McLean S, Ikegaya H. Leg. Med. (Elsevier) 2012; 14(5): 229-238.

Affiliation

Department of Forensic Medicine, Kyoto Prefectural University of Medicine, Kawaramachi, Kamigyo-ku, Kyoto 602-8566, Japan.

Copyright

(Copyright © 2012, Japanese Society of Legal Medicine, Publisher Elsevier Publishing)

DOI

10.1016/j.legalmed.2012.03.005

PMID

22546249

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 (20mg/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 24h. 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 8h. Rotenone-exposed mice showed a suppression of voluntary alcohol intake at 4 and 8h, but total daily alcohol intake did not differ significantly between the two groups. The effects of chronic exposure to rotenone (1, 5, 10 and 20mg/kg, p.o. for 30days) on the alcohol drinking behavior and monoamine levels of rotenone-exposed mice (10mg/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 (10mg/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 (10mg/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.

Language: en