It has been known that the reinforcing effects and long-term consequences of
morphine are closely associated with nucleus accumbens (NAc) in the brain, a key region of the mesolimbic
dopamine pathway. However, the
proteins involved in neuroadaptive processes and
withdrawal symptom in primates of
morphine dependence have not been well explored. In the present study, we performed
proteomes in the NAc of rhesus monkeys of
morphine dependence and withdrawal intervention with
clonidine or
methadone. Two-dimensional electrophoresis was used to compare changes in cytosolic
protein abundance in the NAc. We found a total of 46
proteins differentially expressed, which were further identified by mass spectrometry analysis. The identified
proteins can be classified into 6 classes: metabolism and mitochondrial function, synaptic transmission,
cytoskeletal proteins, oxidative stress, signal transduction and
protein synthesis and degradation. Importantly, we discovered 14
proteins were significantly but similarly altered after withdrawal
therapy with
clonidine or
methadone, revealing potential pharmacological strategies or targets for the treatment of
morphine addiction. Our study provides a comprehensive understanding of the neuropathophysiology associated with
morphine addiction and withdrawal
therapy in primate, which is helpful for the development of
opiate withdrawal
pharmacotherapies.