ArticleAlcoholism, clinical and experimental research2014
Alcohol-preferring rats show decreased corticotropin-releasing hormone-2 receptor expression and differences in HPA activation compared to alcohol-nonpreferring rats.
Article in Alcoholism, clinical and experimental research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 20 citations in OpenAlex.
- Hunting for Genes Underlying Emotionality in the Laboratory Rat: Maps, Tools and Traps.Current neuropharmacology · 2023Review
- Article
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Corticotropin-Releasing Factor (CRF) Neurocircuitry and Neuropharmacology in Alcohol Drinking.Handbook of experimental pharmacology · 2018Review
- CRF modulates glutamate transmission in the central amygdala of naïve and ethanol-dependent rats.Neuropharmacology · 2017Article
- Analyses of differentially expressed genes after exposure to acute stress, acute ethanol, or a combination of both in mice.Alcohol (Fayetteville, N.Y.) · 2017Article
- Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight.Journal of genetics and genomics = Yi chuan xue bao · 2016Article
- A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction.International review of neurobiology · 2016Review
- 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.Pharmacology, biochemistry, and behavior · 2015Article
- β-Endorphin neuronal transplantation into the hypothalamus alters anxiety-like behaviors in prenatal alcohol-exposed rats and alcohol-non-preferring and alcohol-preferring rats.Alcoholism, clinical and experimental research · 2015Article
- Preclinical evidence implicating corticotropin-releasing factor signaling in ethanol consumption and neuroadaptation.Genes, brain, and behavior · 2015Review
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundCorticotropin-releasing hormone (CRH) and urocortins (UCNs) bind to corticotropin-releasing hormone type 2 receptor (CRF2 receptor ), a Gs protein-coupled receptor that plays an important role in modulation of anxiety and stress responses. The Crhr2 gene maps to a quantitative trait locus (QTL) for alcohol preference on chromosome 4 previously identified in inbred alcohol-preferring (iP) and-nonpreferring (iNP) F2 rats.
methodsReal-time polymerase chain reaction was utilized to screen for differences in Crhr2 mRNA expression in the central nervous system (CNS) of male iP and iNP rats. DNA sequence analysis was then performed to screen for polymorphism in Crhr2 in order to identify genetic variation, and luciferase reporter assays were then applied to test their functional significance. Next, binding assays were used to determine whether this polymorphism affected CRF2 receptor binding affinity as well as CRF2 receptor density in the CNS. Finally, social interaction and corticosterone levels were measured in the P and NP rats before and after 30-minute restraint stress.
resultsCrhr2 mRNA expression studies found lower levels of Crhr2 mRNA in iP rats compared to iNP rats. In addition, DNA sequencing identified polymorphisms in the promoter region, coding region, and 3'-untranslated region between the iP and iNP rats. A 7 bp insertion in the Crhr2 promoter of iP rats altered expression in vitro as measured by reporter assays, and we found that CRF2 receptor density was lower in the amygdala of iP as compared to iNP rats. Male P rats displayed decreased social interaction and significantly higher corticosterone levels directly following 30-minute restraint when compared to male NP rats.
conclusionsThis study identified Crhr2 as a candidate gene of interest underlying the chromosome 4 QTL for alcohol consumption that was previously identified in the P and NP model. Crhr2 promoter polymorphism is associated with reduced mRNA expression in certain brain regions, particularly the amygdala, and lowered the density of CRF2 receptor in the amygdala of iP compared to iNP rats. Together, these differences between the animals may contribute to the drinking disparity as well as the anxiety differences of the P and NP rats.
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