Corticosterone Levels and Glucocorticoid Receptor Gene Expression in High Drinking in the Dark Mice and Their Heterogeneous Stock (HS/NPT) Founder Line

Savarese, Antonia M.; Grigsby, Kolter B.; Jensen, Bryan E.; Borrego, Marissa B.; Finn, Deborah A.; Crabbe, John C.; Ozburn, Angela R.

doi:10.3389/fnbeh.2022.821859

Cited by 7 publications

(5 citation statements)

References 66 publications

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“…Interestingly, we also found that acute alcohol injection increased the mRNA brain expression of Fkbp5, in line with previous reports [32][33][34] . We further show that this effect did not depend on the alcohol-drinking history of the mice, nor did we find significant effects of long-term alcohol consumption on this gene's expression.…”

Section: Retrieval Of Alcohol Memories Via An Odor-taste Cue Does Not...supporting

confidence: 93%

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Involvement of FKBP5, but not of stress, in alcohol memory reconsolidation

Rahamim,

Aronovici,

Liran

et al. 2023

Preprint

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Relapse is a fundamental challenge in drug addiction, often evoked by exposure to drug-associated cues. Upon retrieval, memories become temporarily labile before re-stabilizing in a process termed reconsolidation. Therefore, targeting the reconsolidation process offers a therapeutic approach for relapse prevention via the disruption of the drug-cue memories. We recently demonstrated that retrieval of contextual alcohol memories increased the expression of the mRNA encoding for FK506 binding protein 51 (FKBP51), a regulator of the hypothalamic-pituitary-adrenal (HPA) axis. Here, we explored the role of the HPA axis, and FKBP5/FKBP51 in particular, in the reconsolidation of alcohol memories. We found that the FKBP51 inhibitor SAFit2 given before alcohol-memory retrieval using contextual cues prevented the extinction of alcohol place preference behavior in female mice, suggesting that this protein may play a role in cognitive flexibility in a sex-dependent manner. Conversely, the retrieval of alcohol memories using an odor-taste cue did not affectFkbp5expression in rats with a history of chronic alcohol consumption, suggesting that FKBP5 may play a differential role in different alcohol-associated memories. In addition, we provide evidence for HPA axis activation following alcohol memory retrieval, by showing that exposure to an alcohol-associated context led to elevated corticosterone secretion. However, we found that the reconsolidation process was unaffected by HPA axis-related manipulations, namely stress exposure, and administration of corticosterone or the glucocorticoid receptors inhibitor, mifepristone. Our results suggest that although FKBP5 can affect cognitive flexibility, and thereby impact the reconsolidation of alcohol memories, this effect is not likely mediated by HPA axis-related mechanisms.

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Section: Retrieval Of Alcohol Memories Via An Odor-taste Cue Does Not...supporting

confidence: 93%

“…Within the nucleus, GR acts as a transcription factor, with FKBP5 itself being one of its transcriptional targets 27,30 . Indeed, activation of the HPA axis, triggered by stress 31 or by alcohol exposure [32][33][34] , increases brain FKBP5 expression.…”

Section: Introductionmentioning

confidence: 99%

Involvement of FKBP5, but not of stress, in alcohol memory reconsolidation

Rahamim,

Aronovici,

Liran

et al. 2023

Preprint

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“…Moreover, recent work from Savarese et al found that female and male iHDID-1 mice have higher corticosterone responses to a mild stressor (i.p. injections of ethanol or saline) than HS/Npt mice and show reduced glucocorticoid receptor (GR) gene expression in the nucleus accumbens (NAc; critical role in reinforcing and motivated behaviors) both basally and following ethanol administration (2 g/kg) (Savarese et al, 2022 ). Future work using these mice would help identify potential neurobiological markers of stress-related signaling (i.e.…”

Section: Discussionmentioning

confidence: 99%

Development and implementation of a Dependable, Simple, and Cost-effective (DSC), open-source running wheel in High Drinking in the Dark and Heterogeneous Stock/Northport mice

Grigsby,

Usmani,

Anderson

et al. 2024

Front. Behav. Neurosci.

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Maintaining healthy and consistent levels of physical activity (PA) is a clinically proven and low-cost means of reducing the onset of several chronic diseases and may provide an excellent strategy for managing mental health and related outcomes. Wheel-running (WR) is a well-characterized rodent model of voluntary PA; however, its use in biomedical research is limited by economical and methodical constraints. Here, we showcase the DSC (Dependable, Simple, Cost-effective), open-source running wheel by characterizing 24-h running patterns in two genetically unique mouse lines: inbred High Drinking in the Dark line 1 [iHDID-1; selectively bred to drink alcohol to intoxication (and then inbred to maintain phenotype)] and Heterogeneous Stock/Northport (HS/Npt; the genetically heterogeneous founders of iHDID mice). Running distance (km/day), duration (active minutes/day) and speed (km/hour) at 13-days (acute WR; Experiment 1) and 28-days (chronic WR; Experiment 2) were comparable to other mouse strains, suggesting the DSC-wheel reliably captures murine WR behavior. Analysis of 24-h running distance supports previous findings, wherein iHDID-1 mice tend to run less than HS/Npt mice in the early hours of the dark phase and more than HS/Npt in the late hours of dark phase/early light phase. Moreover, circadian actograms were generated to highlight the broad application of our wheel design across disciplines. Overall, the present findings demonstrate the ability of the DSC-wheel to function as a high-throughput and precise tool to comprehensively measure WR behaviors in mice.

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“…The selective glucocorticoid receptor (GR) antagonist CORT113176 was shown to reduce binge-like ethanol drinking in female and male HDID-1 mice, but not their heterogeneous founders, the HS/Npt [ 74 ]. Recent work by Savarese, Grigsby [ 75 ] found no major differences in basal corticosterone levels between HDID-1 and HS/Npt mice, levels were only compared at one timepoint (during the light cycle, when corticosterone levels are relatively low). It would be interesting to see whether differences in daily glucocorticoid oscillations between HDID-1 and HS/Npt mice exist and whether chronic drinking differentially impacts these rhythms.…”

Section: Discussionmentioning

confidence: 99%

“…RNA isolation and cDNA synthesis was performed according to a previously established method [ 75 ]. Following tissue collection of the NAc, SCN, and VTA, RNA was isolated in Purezol reagent and collected using the Bio-Rad Aurum Total RNA Fatty and Fibrous Tissue Kit.…”

Section: Methodsmentioning

confidence: 99%

Targeting the Maladaptive Effects of Binge Drinking on Circadian Gene Expression

Grigsby

Ledford

Batish

et al. 2022

IJMS

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Previous studies (1) support a role of circadian genes in regulating alcohol intake, and (2) reveal that harmful alcohol use alters circadian rhythms. However, there is minimal knowledge of the effects of chronic alcohol processes on rhythmic circadian gene expression across brain regions important for circadian biology and alcohol intake. Therefore, the present study sought to test the effects of chronic binge-like drinking on diurnal circadian gene expression patterns in the master circadian pacemaker (SCN), the ventral tegmental area (VTA), and the nucleus accumbens (NAc) in High Drinking in the Dark-1 (HDID-1) mice, a unique genetic risk model for drinking to intoxication. Consistent with earlier findings, we found that 8 weeks of binge-like drinking reduced the amplitude of several core circadian clock genes in the NAc and SCN, but not the VTA. To better inform the use of circadian-relevant pharmacotherapies in reducing harmful drinking and ameliorating alcohol’s effects on circadian gene expression, we tested whether the casein kinase-1 inhibitor, PF-67046, or the phosphodiesterase type-4 (an upstream regulator of circadian signalling) inhibitor, apremilast, would reduce binge-like intake and mitigate circadian gene suppression. PF-67046 did not reduce intake but did have circadian gene effects. In contrast, apremilast reduced drinking, but had no effect on circadian expression patterns.

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Corticosterone Levels and Glucocorticoid Receptor Gene Expression in High Drinking in the Dark Mice and Their Heterogeneous Stock (HS/NPT) Founder Line

Cited by 7 publications

References 66 publications

Involvement of FKBP5, but not of stress, in alcohol memory reconsolidation

Involvement of FKBP5, but not of stress, in alcohol memory reconsolidation

Development and implementation of a Dependable, Simple, and Cost-effective (DSC), open-source running wheel in High Drinking in the Dark and Heterogeneous Stock/Northport mice

Targeting the Maladaptive Effects of Binge Drinking on Circadian Gene Expression

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