Dataset Information

The alterations of proteins expression related to insulin signaling pathway in the brain of phenobarbital addictive rats by TMT

ABSTRACT: Drug addiction is a chronic relapsing brain disease. The alterations of glucose uptake and metabolism were 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 dosed escalation and evaluated addiction-related symptoms. We also performed proteomic analysis of the function of the differentially expressed (DE) proteins via bioinformatics in brain tissues by LC-MS/MS on day 60 and 90 of phenobarbital or 0,5% CMC-Na (vehicle) administration. The results showed that phenobarbital addictive rats developed severe withdrawal symptoms after abstinence. Proteomics analysis showed that numerous DE proteins were enriched after phenobarbital administration; which CALM1, ARAF and Cbl proteins (related to insulin signaling pathway) were significantly downregulated on day 60 but no day 90; however, SLC27A3 and NF-kB1 proteins (related to insulin resistance) were significantly upregulated on day 90. Our data indicate that insulin signaling pathway and insulin resistance may play a role in the development of phenobarbital addiction and brain injury and the findings may have important clinical implication.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Guojun Wang

LAB HEAD: Guojun Wang

PROVIDER: PXD021101 | Pride | 2020-10-29

REPOSITORIES: Pride

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Alterations of Glucose Uptake and Protein Expression Related to the Insulin Signaling Pathway in the Brain of Phenobarbital-Addictive Rats by <sup>18</sup>F-FDG PET/CT and Proteomic Analysis.

Wang Maolin M Pu Xiaofeng X Feng Bimin B Fan Qingze Q Dai Yan Y Chen Yue Y Li Ying Y Liu Liang L Cao Shousong S Wang Guojun G

Journal of proteome research 20201026 1

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 <sup>18</sup>F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) ...[more]

PMID: 33105993

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Project description:Drug-induced alterations in transcriptional regulation play a central role in establishing the persistent neuroplasticities that occur during drug addiction. Additionally, changes in gene expression associated with drug administration provide valuable insight into the molecular basis of drug abuse. The molecular mechanisms that underlie susceptibility to psychostimulant addiction remain unknown. Identifying the common gene transcriptional responses to psychostimulants can provide a mechanistic insight to elucidate the molecular nature of drug dependence. Male Wistar rats (4 weeks old) were acclimatized for a week to their housing conditions prior to experiments. Thereafter, they were divided into two groups: (cohort 1) 4 groups of rats (n=12 rats per group) given saline only (i.p., "drug-naive" rats); and (cohort 2): 3 groups of rats given either methamphetamine, amphetamine or methylphenidate (5 mg/kg,i.p., M-CM-"M-bM-^BM-,M-EM-^Sdrug-pretreated") for 7 days (2x daily) prior to behavioral assays. Conditioned place preference (CPP) tests were conducted a day after the final drug administration. Rats which showed CPP were evaluated for self-administration of the psychostimulants. [Cohort 1] A day after the final self-administration test, brains of 2-3 rats from each subgroups (i.e. those which showed the most robust self-administration), as well as 5 rats from the control group were removed for microarray analysis. The striatum (rostral part of the caudate putamen and the nucleus accumbens [NAc]) and the prefrontal cortex were dissected and immediately frozen at -70M-CM-^BM-BM-0C. Total RNA was isolated and gene expression profiling was conducted on independent pools of total RNA from 2-5 animals per group. [Cohort 2] A day after the final self-administration test, brains of 3 rats from each subgroups (i.e. those which showed the most robust self-administration), as well as 3 rats from the control group were removed for microarray analysis. The striatum (rostral part of the caudate putamen and the nucleus accumbens [NAc]) and the prefrontal cortex were dissected and immediately frozen at -70M-BM-0C. Total RNA was isolated and gene expression profiling was conducted on independent pools of total RNA from three animals per group.

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