Proteomic analysis of male rat nucleus accumbens, dorsal hippocampus and amygdala on conditioned place aversion induced by morphine withdrawal

Addiction is characterized by compulsive drug seeking and taking behavior, which is thought to result from persistent neuroadaptations, encoded by changes of gene expression. We previously demonstrated that the changes in synaptic plasticity were required for the formation of aversive memories associated with morphine withdrawal. However, the proteins involved in synaptic plasticity and aversive memory formation have not been well explored. In the present study, we employed a two-dimensional gel electrophoresis (2-DE)-based proteomic technique to detect the changes of protein expression in the nucleus accumbens, amygdala and dorsal hippocampus of the rats that had developed conditioned morphine withdrawal. We found that twenty-three proteins were significantly altered in the amygdala and dorsal hippocampus after conditioned morphine withdrawal. These proteins can be classified into multiple categories, such as energy metabolism, signal transduction, synaptic transmission, cytoskeletal proteins, chaperones, and protein metabolism according to their biological functions. Eight proteins related to synaptic plasticity were further confirmed by western blot analysis. It is very likely that these identified proteins may contribute to conditioned morphine withdrawal-induced neural plasticity and aversive memory formation. Thus, our work will help understand the potential mechanism associated with generation of drug withdrawal memories.