Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking.
- Authors
- McClintick, Jeanette N; McBride, William J; Bell, Richard L; Ding, Zheng-Ming; Liu, Yunlong; Xuei, Xiaoling; Edenberg, Howard J
- Year
- 2015
- Journal
- Pharmacology, biochemistry, and behavior
- PMID
- 25542586
- DOI
- 10.1016/j.pbb.2014.12.007
- PMCID
- PMC4302739
Alcohol binge-drinking during adolescence is a serious public health concern with long-term consequences. We used RNA sequencing to assess the effects of excessive adolescent ethanol binge-drinking on gene expression in the dorsal raphe nucleus (DRN) of alcohol preferring (P) rats. Repeated binges across adolescence (three 1h sessions across the dark-cycle per day, 5 days per week for 3 weeks starting at 28 days of age; ethanol intakes of 2.5-3 g/kg/session) significantly altered the expression of approximately one-third of the detected genes. Multiple neurotransmitter systems were altered, with the largest changes in the serotonin system (21 of 23 serotonin-related genes showed decreased expression) and GABA-A receptors (8 decreased and 2 increased). Multiple neuropeptide systems were also altered, with changes in the neuropeptide Y and corticotropin-releasing hormone systems similar to those associated with increased drinking and decreased resistance to stress. There was increased expression of 21 of 32 genes for potassium channels. Expression of downstream targets of CREB signaling was increased. There were also changes in expression of genes involved in inflammatory processes, axonal guidance, growth factors, transcription factors, and several intracellular signaling pathways. These widespread changes indicate that excessive binge drinking during adolescence alters the functioning of the DRN and likely its modulation of many regions of the central nervous system, including the mesocorticolimbic system.
Distribution of fold changes of genes with an FDR ≤ 0.05.
Overlap of present data with human and other studies using P ratsVenn diagram indicating overlap of differentially expressed genes from this study (within the DRN of adolescent binge ethanol-drinking P rats) with previous P/NP animal studies (includes expression studies of naïve P vs. naïve NP and alcohol treated P vs. controls) and human studies (postmortem expression and GWAS). Specific genes and studies are noted in Supplementary Table 1.
No entities extracted from this document yet.
No uploaded files.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Integrated single-cell multiomic profiling of caudate nucleus suggests key mechanisms in alcohol use disorder. | Green NC et al. | — | 2025 | → |
| Neuropeptide Y1 receptor expressing circuit from the central amygdala to lateral hypothalamus modulates binge-like ethanol consumption in a sex-dependent manner. | Bendrath SC et al. | — | 2025 | → |
| The role of dorsal raphe nucleus neuropeptides in reward and aversion. | Braden K et al. | — | 2025 | → |
| Changes in serotonin neurotransmission as assayed by microdialysis after acute, intermittent or chronic ethanol administration and withdrawal. | Dahchour A et al. | — | 2024 | → |
| The CRF/Urocortin systems as therapeutic targets for alcohol use disorders. | Favoretto CA et al. | — | 2024 | → |
| Brain proteomic atlas of alcohol use disorder in adult males. | Teng PN et al. | — | 2023 | → |
| Cross talk about the role of Neuropeptide Y in CNS disorders and diseases. | Bale R et al. | — | 2023 | → |
| Modulation of neuronal excitability by binge alcohol drinking. | Gimenez-Gomez P et al. | — | 2023 | → |
| Sex differences in susceptibility to substance use disorder: Role for X chromosome inactivation and escape? | Krueger K et al. | — | 2023 | → |
| <i>α</i>6-Containing GABA<sub>A</sub> Receptors: Functional Roles and Therapeutic Potentials. | Sieghart W et al. | — | 2022 | → |
| DNA methylation of Vesicular Glutamate Transporters in the mesocorticolimbic brain following early-life stress and adult ethanol exposure-an explorative study. | Vrettou M et al. | — | 2021 | → |
| Effects of adolescent substance use disorders on central cholinergic function. | Hauser SR et al. | — | 2021 | → |
| Effects of chronic intermittent ethanol exposure and withdrawal on neuroblastoma cell transcriptome. | McClintick JN et al. | — | 2020 | → |
| MicroRNA-34a Regulates the Depression-like Behavior in Mice by Modulating the Expression of Target Genes in the Dorsal Raphè. | Lo Iacono L et al. | — | 2020 | → |
| mTORC1 pathway is involved in the kappa opioid receptor activation-induced increase in excessive alcohol drinking in mice. | Zhou Y et al. | — | 2020 | → |
| Pharmacotherapeutic management of co-morbid alcohol and opioid use. | Hood LE et al. | — | 2020 | → |
| Ethanol activates immune response in lymphoblastoid cells. | McClintick JN et al. | — | 2019 | → |
| Genetic, Psychological, and Personal Network Factors Associated With Changes in Binge Drinking Over 2 Years Among Mexican Heritage Adolescents in the USA. | Song S et al. | — | 2019 | → |
| Genetic Selection for Alcohol Preference in Mice Alters Dorsal Striatum Neurotransmission. | Fritz BM et al. | — | 2019 | → |
| Hippocampal transcriptome reveals novel targets of FASD pathogenesis. | Lunde-Young R et al. | — | 2019 | → |
| Peri-adolescent alcohol consumption increases sensitivity and dopaminergic response to nicotine during adulthood in female alcohol-preferring (P) rats: Alterations to α7 nicotinic acetylcholine receptor expression. | Waeiss RA et al. | — | 2019 | → |
| Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats. | Ruiz P et al. | — | 2018 | → |
| Assessment of depression-like behavior and anhedonia after repeated cycles of binge-like ethanol drinking in male C57BL/6J mice. | Olney JJ et al. | — | 2018 | → |
| Examining the effects of alcohol on GABA<sub>A</sub> receptor mRNA expression and function in neural cultures generated from control and alcohol dependent donor induced pluripotent stem cells. | Lieberman R et al. | — | 2018 | → |
| Gene expression changes in the ventral hippocampus and medial prefrontal cortex of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking. | McClintick JN et al. | — | 2018 | → |
| Persistent Neuroadaptations in the Expression of Genes Involved in Cholesterol Homeostasis Induced by Chronic, Voluntary Alcohol Intake in Rats. | Alsebaaly J et al. | — | 2018 | → |
| Adolescent intermittent ethanol reduces serotonin expression in the adult raphe nucleus and upregulates innate immune expression that is prevented by exercise. | Vetreno RP et al. | — | 2017 | → |
| Chronic Ethanol During Adolescence Impacts Corticolimbic Dendritic Spines and Behavior. | Jury NJ et al. | — | 2017 | → |
| GABA<sub>A</sub> receptor subtype involvement in addictive behaviour. | Stephens DN et al. | — | 2017 | → |
| Rat animal models for screening medications to treat alcohol use disorders. | Bell RL et al. | — | 2017 | → |
| The Role of Neuropeptide Y (NPY) in Alcohol and Drug Abuse Disorders. | Robinson SL et al. | — | 2017 | → |
| A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction. | Bell RL et al. | — | 2016 | → |
| An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence. | Quadros IM et al. | — | 2016 | → |
| Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings. | Bell RL et al. | — | 2016 | → |
| Gene Expression Changes in Glutamate and GABA-A Receptors, Neuropeptides, Ion Channels, and Cholesterol Synthesis in the Periaqueductal Gray Following Binge-Like Alcohol Drinking by Adolescent Alcohol-Preferring (P) Rats. | McClintick JN et al. | — | 2016 | → |
| Alcohol and violence: neuropeptidergic modulation of monoamine systems. | Miczek KA et al. | — | 2015 | → |
| Neurogenetics and gene therapy for reward deficiency syndrome: are we going to the Promised Land? | Blum K et al. | — | 2015 | → |
| Novel candidate genes for alcoholism--transcriptomic analysis of prefrontal medial cortex, hippocampus and nucleus accumbens of Warsaw alcohol-preferring and non-preferring rats. | Stankiewicz AM et al. | — | 2015 | → |