The effects of sodium butyrate,an inhibitor of histone deacetylase,on the cocaine- and sucrose-maintained self-administration in rats |
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Authors: | Jie Sun Lei Wang Baohong Jiang Bin HuiZhigang Lv Lan Ma |
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Institution: | Pharmacology Research Center and State Key Laboratory of Medical Neurobiology, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China |
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Abstract: | In order to substantiate the concept that cocaine behavioral effects may be influenced by histone modification, rats were trained to self-administer cocaine intravenously (0.75 mg/(kg injection)), and were systemically pretreated with sodium butyrate (NaBu), a potent histone deacetylase inhibitor, before the test session during the maintenance phase. The effect of NaBu on a control reinforcer (sucrose)-induced self-administration was also assessed. NaBu (100–200 mg/kg) was inactive in altering the cocaine (0.75 mg/(kg injection))-maintained responding and at the highest dose (400 mg/kg) it did increase cocaine-induced lever presses during the maintenance phase. On the other hand, sucrose-reinforcing potential was not altered when NaBu was given at the highest dose (400 mg/kg). These findings extend previous observations that changes in histone acetylation are relevant to cocaine-induced behavioral effects. Given that histone acetylase inhibitor enhances cocaine-induced behavioral plasticity, the therapeutic benefits of histone acetyltransferase inhibitors warrant further investigation in the experimental models of cocaine abuse. |
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Keywords: | Sodium butyrate Histone deacetylase inhibitor Cocaine Self-administration Addiction |
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