Evidence map›Paper›PMID 33606281›Full record

ArticleAlcoholism, clinical and experimental research2021

Antisense-Induced Downregulation of Clock Genes in the Shell Region of the Nucleus Accumbens Reduces Binge Drinking in Mice.

Rishi Sharma, Hunter Puckett, Micaela Kemerling, Meet Parikh, Pradeep Sahota, Mahesh Thakkar

Abstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
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  4. International journal of molecular sciences · 2022
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Rishi SharmaHarry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Columbia, MO, USA.
Hunter PuckettHarry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Columbia, MO, USA.
Micaela KemerlingHarry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Columbia, MO, USA.
Meet ParikhHarry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Columbia, MO, USA.
Pradeep SahotaHarry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Columbia, MO, USA.
Mahesh ThakkarHarry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Columbia, MO, USA.ORCID 0000-0001-6876-9850

Funding

Neuronal mechanisms mediating the effects of chronic alcohol consumption on sleep homeostasis.R01AA028175 · NIAAA · UNIVERSITY OF MISSOURI-COLUMBIA · PI THAKKAR, MAHESH M · 2019 to 2023
$1.8M
Sleep and PTSDI01BX002661 · VA · HARRY S. TRUMAN MEMORIAL VA HOSPITAL · PI SAHOTA, PRADEEP KUMAR · 2016 to 2023
–
BLRD VA I01 BX002661Center for Integrated Healthcare, U.S. Department of Veterans Affairs I01BX002661Foundation for the National Institutes of Health AA028175-01NIAAA NIH HHS R01 AA028175
6 · The paper itself

Abstract

introductionsBinge drinking is a deadly pattern of alcohol consumption. Evidence suggests that genetic variation in clock genes is strongly associated with alcohol misuse; however, the neuroanatomical basis for such a relationship is unknown. The shell region of the nucleus accumbens (NAcSh) is well known to play a role in binge drinking. Hence, we examined whether clock genes in the NAcSh regulate binge drinking.

methodsTo address this question, 2 experiments were performed on male C57BL/6J mice. In the first experiment, mice exposed to alcohol or sucrose under the 4-day drinking-in-the-dark (DID) paradigm were euthanized at 2 different time points on day 4 [7 hours after light (pre-binge drinking) or dark (post-binge drinking) onset]. The brains were processed for RT-PCR to examine the expression of circadian clock genes (Clock, Per1, and Per2) in the NAcSh and suprachiasmatic nucleus (SCN). In the second experiment, mice were exposed to alcohol, sucrose, or water as described above. On day 4, 1 hour prior to the onset of alcohol exposure, mice were bilaterally infused with either a mixture of circadian clock gene antisense oligodeoxynucleotides (AS-ODNs; antisense group) or nonsense/random ODNs (R-ODNs; control group) through surgically implanted cannulas above the NAcSh. Alcohol/sucrose/water consumption was measured for 4 hours. Blood alcohol concentration was measured to confirm binge drinking. Microinfusion sites were histologically verified using cresyl violet staining.

resultsAs compared to sucrose, mice euthanized post-binge drinking (not pre-binge drinking) on day 4 displayed a greater expression of circadian genes in the NAcSh but not in the SCN. Knockdown of clock genes in the NAcSh caused a significantly lower volume of alcohol to be consumed on day 4 than in the control treatment. No differences were found in sucrose or water consumption.

conclusionsOur results suggest that clock genes in the NAcSh play a crucial role in binge drinking.

Indexed as

AnimalsBinge DrinkingCircadian ClocksCircadian RhythmCLOCK ProteinsDown-RegulationEthanolMaleMiceMice, Inbred C57BLMicroinjectionsNucleus AccumbensOligonucleotides, AntisensePeriod Circadian ProteinsClock protein, mouseCLOCK ProteinsEthanolOligonucleotides, AntisensePer1 protein, mousePer2 protein, mousePeriod Circadian ProteinsBinge drinkingClockNucleus accumbensPer1Per2

Identifiers

PMID33606281
PMCPMC8535763

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.