Drug addiction is a chronic relapsing
brain disease. Alterations of
glucose uptake and metabolism are found in the brain of drug addicts.
Insulin mediates brain
glucose metabolism and its abnormality could induce
brain injury and
cognitive impairment. Here, we established a rat model of
phenobarbital addiction by 90 days of dose escalation and evaluated addiction-related symptoms. We also performed 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to detect
glucose uptake in the brain and proteomic analysis of the function of the differentially expressed (DE)
proteins via bioinformatics in brain tissues by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) on days 60 and 90 of
phenobarbital or 0.5%
carboxymethyl cellulose sodium (CMC-Na) (vehicle) administration. The results showed that
phenobarbital-addictive rats developed severe
withdrawal symptoms after abstinence and
glucose uptake was significantly increased in the brain. Proteomics analysis showed that numerous DE
proteins were enriched after
phenobarbital administration, among which CALM1, ARAF, and Cbl
proteins (related to the
insulin signaling pathway) were significantly downregulated on day 60 but not day 90. However, SLC27A3 and NF-κB1
proteins (related to
insulin resistance) were significantly upregulated on day 90 (data are available via ProteomeXchange with identifier PXD021101). Our data indicate that the
insulin signaling pathway and
insulin resistance may play a role in the development of
phenobarbital addiction and
brain injury, so the findings may have important clinical implications.