iTRAQ proteomic analysis of the anterior insula in morphine-induced conditioned place preference rats with high-frequency deep brain stimulation intervention.

Morphine dependence or addiction is a serious global public health and social problem, and traditional treatments are very limited. Deep brain stimulation (DBS) has emerged as a new potential treatment for drug addiction. Repeated use of morphine leads to neuroadaptive and molecular changes in the addiction-related brain regions. We have previously performed isobaric tags for relative and absolute quantitation (iTRAQ) labelling coupled with 2D-LC MS/MS in anterior insular samples from rats treated with saline control, morphine or morphine plus DBS, and the identified expression of eight proteins are altered by morphine and reversed by high-frequency DBS (HF-DBS). In this study, we analysed the proteomic data in more details. A total of 5575 proteins were identified. Relative to the saline group, the morphine group showed 14 down-regulated and three up-regulated proteins. There were 118 proteins increased and 87 proteins decreased between DBS implanted animals and morphine group. Several differentially expressed proteins were verified with parallel reaction monitoring (PRM) assay. Based on Gene Ontology enrichment an KEGG pathway analyses, the majority of these differentially expressed proteins (DEPs) were involved in protein metabolic process, G-protein coupled receptor signalling pathway, calcium-mediated signalling, neurotransmitter transport, dopaminergic synapse and mTOR signalling pathway. These data offer a comprehensive understanding of the proteomic changes associated with morphine addiction and DBS therapy in addicted animal models, which is important for the development of DBS interventions for drug addiction.