Evidence map›Paper›PMID 33683478›Full record

ArticleInternational journal of bipolar disorders2021

Prefrontal dopamine D1 receptor manipulation influences anxiety behavior and induces neuroinflammation within the hippocampus.

Dominik K E Beyer, Annika Mattukat, Nadja Freund

Open access · goldAbstract read
In one paragraph

Article in International journal of bipolar disorders, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 37% of its field
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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

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  6. Consequences of adolescent drug use.Translational psychiatry · 2023
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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

3 authors at 2 institutions in 1 country.

Dominik K E BeyerDivision of Experimental and Molecular Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL University Hospital, Ruhr-University, Alexandrinenstr.1, 44791, Bochum, Germany.
Annika MattukatDivision of Experimental and Molecular Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL University Hospital, Ruhr-University, Alexandrinenstr.1, 44791, Bochum, Germany.
Nadja FreundDivision of Experimental and Molecular Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL University Hospital, Ruhr-University, Alexandrinenstr.1, 44791, Bochum, Germany. Nadja.freund@rub.de.ORCID http://orcid.org/0000-0002-5337-6680
LWL-Universitätsklinikum Bochum · DEUniversity Hospitals of the Ruhr-University of Bochum · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPrefrontal dopamine D1 receptor (D1R) mediates behavior related to anxiety, reward and memory, and is involved in inflammatory processes, all of which are affected in bipolar disorder. Interleukin-6 (IL-6), a pro-inflammatory cytokine, is increased in patients with bipolar disorder in plasma samples, imaging studies and postmortem tissue and is an indicator for an inflammatory state. We could previously show that lentiviral overexpression of D1R in the medial prefrontal cortex (mPFC) of male adult rats and its termination induces bipolar disorder-like behavior. The purpose of this study was to investigate anxiety and the role of the immune system, specifically IL-6 positive neurons in this animal model. Due to its high density of inflammatory mediator receptors and therewith sensibility to immune activation, the hippocampus was investigated.

methodsExpression of the gene for D1R in glutamatergic neurons within the mPFC of male, adult rats was manipulated through an inducible lentiviral vector. Animals over-expressing the gene (mania-like state), after termination of the expression (depressive-like) and their respective control groups were investigated. Anxiety behavior was studied in the elevated plus maze and marble burying test. Furthermore, IL-6-positive cells were counted within several subregions of the hippocampus.

resultsD1R manipulation in the mPFC had only mild effects on anxiety behavior in the elevated plus maze. However, subjects after termination buried more marbles compared to D1R over-expressing animals and their respective control animals indicating elevated anxiety behavior. In addition, animals in the depressive-like state showed higher numbers of IL-6 positive cells reflecting an elevated pro-inflammatory state in the hippocampus, in the CA3 and dentate gyrus. Consistently, inflammatory state in the whole hippocampus and anxiety behavior correlated positively, indicating a connection between anxiety and inflammatory state of the hippocampus.

conclusionsBehavioral and neurobiological findings support the association of manipulation of the D1R in the mPFC on anxiety and inflammation in the hippocampus. In addition, by confirming changes in the inflammatory state, the proposed animal model for bipolar disorder has been further validated.

Indexed as

AnxietyBipolar disorderInterleukin-6LentivirusPrefrontal cortexRat

Identifiers

PMID33683478
PMCPMC7940461
OpenAlexW3135000943

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Registered trials

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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.