Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state

In the present study, we investigated the changes in protein expression and redox state in selected parts of the rat brain induced by 4 weeks of administration of relatively low doses (10 mg/kg per day) of morphine. Using label-free quantitative proteomic analysis, we found some specific changes in protein expression profiles in the cortex, hippocampus, striatum, and cerebellum the day after morphine discontinuation and 1 week later. Interestingly, protein expression after seven days of morphine withdrawal was not significantly different from that detected one day after the last drug dose in any of the brain regions studied. In parallel with some changes in protein expression, we found a significant reduction in lipid peroxidation, most of which persisted for a week after morphine was discontinued. Treatment with morphine resulted in a significant increase in complex II in the cortex, which was accompanied by increased protein carbonylation, in contrast to the other brain regions studied. Glutathione levels were altered differently in different brain regions after morphine treatment. Our data suggest that long-term treatment with morphine specifically affects different brain regions and that a one-week withdrawal of the drug is not sufficient to normalize protein levels and cellular redox state.