Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 52, Issue 7, Pages 1218-1227Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2012.01.004
Keywords
Morphine; Thioredoxin-1; Heat shock protein 70; Geranylgeranylacetone; Free radicals
Funding
- National Natural Science Foundation of China [30860085]
- Young and Middle-Aged Academic Leaders of Yunnan Province [2006PY01-07]
- Foundation for Excellent Doctor Degree Dissertations of Kunming University of Science and Technology
- Key Laboratory of Medical Neurobiology, Kunming University of Science and Technology
- Grants-in-Aid for Scientific Research [23390152] Funding Source: KAKEN
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There are few efficacious interventions to combat morphine dependence. Thioredoxin-1 (Trx-1) and heat shock protein 70 (Hsp70) are emerging as important modulators of neuronal function. They have been shown to be involved in cellular protective mechanisms against a variety of toxic stressors. This study was designed to investigate the effects of geranylgeranylacetone (GGA), a pharmacological inducer of Trx-1 and Hsp70, on morphine-induced hyperlocomotion, rewarding effect, and withdrawal syndrome. Trx-1 and Hsp70 expression was increased in the frontal cortex, hippocampus, ventral tegmental area, and nucleus accumbens of mice after GGA treatment. GGA administration reduced morphine-induced motor activity and inhibited conditioned place preference. GGA markedly attenuated the morphine-naloxone-induced withdrawal signs, including jumping, rearing, and forepaw tremor. Furthermore, the activation of cAMP-responsive element-binding protein and the expression of Delta FosB and cyclin-dependent kinase 5 were decreased in the nucleus accumbens by GGA treatment after morphine withdrawal. In the nucleus accumbens, GGA enhanced morphine-induced expression of Trx-1 and Hsp70 after morphine withdrawal. These results suggest that strengthening the expression of Trx-1 and Hsp70 in the brain by using noncytotoxic pharmacological inducers may provide a novel therapeutic strategy for morphine dependence. GGA could be a safe and novel therapeutic agent for morphine dependence. (C) 2012 Elsevier Inc. All rights reserved.
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