Gene expression in the addicted brain.
paper
Cited
Public
- Authors
- Zhou, Zhifeng; Enoch, Mary-Anne; Goldman, David
- Year
- 2014
- Journal
- International review of neurobiology
- PMID
- 25172478
- DOI
- 10.1016/B978-0-12-801105-8.00010-2
- PMCID
- PMC4427035
Addiction is due to changes in the structure and function of the brain, including neuronal networks and the cells that comprise them. Within cells, gene expression changes can track and help explain their altered function. Transcriptional changes induced by addictive agents are dynamic and divergent and range from signal pathway-specific perturbations to widespread molecular and cellular dysregulation that can be measured by "omic" methods and that can be used to identify new pathways. The molecular effects of addiction depend on timing of exposure or withdrawal, the stage of adaptation, the brain region, and the behavioral model, there being many models of addiction. However, the molecular neural adaptations across different drug exposures, conditions, and regions are to some extent shared and can reflect common actions on pathways relevant to addiction. Epigenetic studies of DNA methylation and histone modifications and studies of regulatory RNA networks have been informative for elucidating the mechanisms of transcriptional change in the addicted brain.
Differentially expressed genes in the hippocampus of cocaine- and alcohol-addicted individuals, as detected by RNA-Seq. (A) Scatter plot of –log10 P (uncorrected P value) versus FDR q value for all 16,008 expressed genes. FDR thresholds of 0.2 and 0.05 are marked, as well as corresponding uncorrected P values at an FDR of 0.2. (B) Genes differentially expressed (FDR <0.2) in cocaine only, alcohol only, and common to both. (C) Genes with significant differential expression (FDR <0.2) observed in both chronic cocaine- and alcohol-addicted individuals.
Differential gene expression in hippocampus of P and NP rats. (A) Hippocampal Grm2 mRNA levels in P and NP rats. (B) Western blot of hippocampal mGluR2 protein in NP and P rats (2 individuals in each group). (C) Average expression levels (normalized log2 read counts, upper left) of 11,406 genes measured by RNA-Seq are compared between P and NP rats. The fold change (P vs. NP) and nominal P values (–log10, t test) for each gene are also plotted (lower left). Significance of difference between P and NP for each gene is color coded: blue (black in the print version), not significant; orange (dark gray in the print version), P<0.05; green (light gray in the print version), false discovery rate <0.05. Fifteen differentially expressed genes among those in the over represented functional domains are highlighted and details of their expression differences are listed in the table (right).
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| Name | Type |
|---|---|
| 3,4-methylenedioxymethamphetamine | drug |
| Absent GRM2 protein local | phenotype |
| Acute drug exposure local | drug |
| ADCY | gene |
| ADCY1 | gene |
| addicted brain local | phenotype |
| Addicted brain local | anatomy |
| addiction | phenotype |
| Addiction behaviors local | phenotype |
| addiction-related gene transcription local | phenotype |
| Addictive agents local | drug |
| adrenal local | anatomy |
| Adrenergic | drug |
| alcohol | phenotype |
| alcohol abuse | phenotype |
| alcohol dependence | phenotype |
| Alcohol-drinking behavior local | phenotype |
| Alcohol-drinking behaviors local | phenotype |
| alcoholism | phenotype |
| alcohol preference | phenotype |
| Alcohol seeking | phenotype |
| Alcohol vapor local | drug |
| amphetamine | drug |
| angiogenesis | phenotype |
| apoptosis | phenotype |
| AQP11 local | gene |
| ARC | gene |
| axon guidance local | phenotype |
| Bdnf | gene |
| bed nucleus of the stria terminalis | anatomy |
| behavioral sensitization | phenotype |
| behavioral sensitization to morphine local | phenotype |
| BEX1 local | gene |
| BEX2 local | gene |
| BEX3 local | gene |
| BEX4 | gene |
| BEX5 local | gene |
| brain | anatomy |
| brain glucose metabolism | phenotype |
| CACNB2 | gene |
| calcium/calmodulin-dependent protein kinase local | gene |
| Calm1 | gene |
| CALM2 local | gene |
| CAMK2A | gene |
| CAMK2D | gene |
| CART | gene |
| CARTPT | gene |
| Cdk5 | gene |
| CDR1 local | gene |
| Cell adhesion molecules local | gene |
| cerebellar degeneration | phenotype |
| cholinergic | drug |
| chronic cocaine abusers | phenotype |
| Chronic drug exposure local | drug |
| chronic heroin abusers local | cohort |
| CIR local | gene |
| CNS | anatomy |
| cocaine | phenotype |
| cocaine addict local | phenotype |
| Cocaine addict cohort local | cohort |
| control rats | cohort |
| controls | cohort |
| craving | phenotype |
| CREB1 | gene |
| cue-induced reinstatement | phenotype |
| decreased MBP-immunoactive oligodendrocytes local | phenotype |
| dentate gyrus | anatomy |
| Dnmt3a | gene |
| Dnmt3b | gene |
| dopamine receptor local | gene |
| Dopaminergic transmission genes local | gene |
| Dopamine transporter | drug |
| dorsal striatum | anatomy |
| DRD1 | gene |
| drug | drug |
| drug dependence | phenotype |
| drug-free control local | phenotype |
| drug response genes local | phenotype |
| drug-reward behavior local | phenotype |
| Drug-reward behavior local | phenotype |
| drugs | drug |
| drug-seeking behavior | phenotype |
| Drug self-administration local | drug |
| DUSP1 local | gene |
| Egr1 | gene |
| Endogenous retroviruses local | drug |
| ERF | gene |
| Ethanol locomotor sensitivity local | phenotype |
| extended amygdala | anatomy |
| extracellular matrix integrity local | phenotype |
| F2 rats local | cohort |
| FAM123A local | gene |
| Fos | gene |
| Fosb | gene |
| functional variant | variant |
| G9a local | gene |
| GABA | phenotype |
| GABAergic transmission genes local | gene |
| Gabbr1 | gene |
| Gabrg2 | gene |
| gene-based manipulations local | drug |
| glutamate | drug |
| Glutamate hyperfunction local | phenotype |
| Glutamatergic transmission genes local | gene |
| Gphn | gene |
| GRIN2B | gene |
| GRM2 | gene |
| Grm2 C407* local | variant |
| GRM2 C407* local | variant |
| Grm2 knockout mice local | cohort |
| GRM2 stop codon allele local | variant |
| GRM3 | gene |
| H3K4me3 | drug |
| Hdac1 | gene |
| HDAC2 local | gene |
| HDAC5 | gene |
| heavy drinking | phenotype |
| heroin abusers local | cohort |
| hippocampus | anatomy |
| HIST1H4E local | gene |
| HIVEP3 local | gene |
| Homer1 | gene |
| HPA axis | anatomy |
| human chronic cocaine brains local | cohort |
| humans | cohort |
| hypothalamus | anatomy |
| Igf1r | gene |
| Impaired synaptic depression local | phenotype |
| infralimbic cortex | anatomy |
| INSR local | gene |
| ion transport local | phenotype |
| Jun | gene |
| KCNJ5 local | gene |
| Lentiviral vector expressing GRM2 local | drug |
| let-7 local | gene |
| lncRNAs | drug |
| long-term memory | phenotype |
| long-term potentiation | phenotype |
| Long-term potentiation genes local | gene |
| LRCH4 local | gene |
| LY341495 | drug |
| LY379268 | drug |
| MBP | gene |
| MeCP2 | gene |
| mesolimbic system | anatomy |
| mGluR2/3 agonist local | drug |
| mGluR2 stop codon local | variant |
| Midbrain ventral tegmental area local | anatomy |
| miR-133b local | gene |
| miR-8 family local | gene |
| Mitochondrial inner membrane genes local | gene |
| MMP9 | gene |
| MOBP | gene |
| monkeys | cohort |
| morphine | drug |
| motivation for cocaine local | phenotype |
| myelin-related genes local | gene |
| NAc | anatomy |
| NDUFA12L local | gene |
| NDUFS2 local | gene |
| neural adaptations local | phenotype |
| Neural circuitries local | anatomy |
| neurodegeneration | phenotype |
| neurodegenerative diseases | phenotype |
| neurogenesis | phenotype |
| NFKB1 | gene |
| NF-κB | gene |
| nicotine | drug |
| Non-active abusers local | cohort |
| NP rats | cohort |
| NPTX2 local | gene |
| NRAS local | gene |
| nucleus accumbens | anatomy |
| Nur local | gene |
| opioid | drug |
| opioid tolerance | phenotype |
| OPRM1 | cohort |
| Oxidative phosphorylation genes local | gene |
| PAPD1 local | gene |
| PCDHA7 local | gene |
| Persistent behavioral changes local | phenotype |
| pharmacological challenges local | drug |
| pituitary gland | anatomy |
| PNOC | gene |
| Pomc | gene |
| Post-dependent rats local | cohort |
| postmortem brain | anatomy |
| Postmortem brain tissues local | anatomy |
| Pp1c local | gene |
| PPP1CB local | gene |
| PPP1CC local | gene |
| PPP3CA | gene |
| P rats | cohort |
| prefrontal cortex | anatomy |
| presynaptic release genes local | gene |
| PRKCB1 local | gene |
| protein kinase A | drug |
| protein phosphatase local | gene |
| Proteolipid protein local | gene |
| Recent active cocaine abusers local | cohort |
| RECK local | gene |
| Reduced GRM2 transcript local | phenotype |
| response | phenotype |
| RNA processing genes local | gene |
| Rnd gene family local | gene |
| rodents | cohort |
| short-term memory | phenotype |
| signal transduction | phenotype |
| Slc6a15 | gene |
| SLC6A3 | gene |
| striatum | anatomy |
| substance abuse | phenotype |
| SYPL2 local | gene |
| tegmental area local | anatomy |
| Th | gene |
| transcriptional regulation local | phenotype |
| translational regulation local | phenotype |
| UQCRB local | gene |
| ventral tegmental area | anatomy |
| vulnerability | phenotype |
| Wistar rats | cohort |
| withdrawal | phenotype |
| zebrafish embryos local | cohort |
| ZGPAT local | gene |
| Zhou2011 hippocampal cohort local | cohort |
| Δ-FosB local | gene |
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|---|---|---|
| The genetic epidemiology of substance use disorder: A review. | 2017 | 28938182 |
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