Evidence map›Paper›PMID 39684680›Full record

ArticleInternational journal of molecular sciences2024

A Risk Factor for Attention Deficit Hyperactivity Disorder Induces Marked Long-Term Anatomical Changes at GABAergic-Dopaminergic Synapses in the Rat Ventral Tegmental Area.

Steve Seo, Louise C Parr-Brownlie, Hollie E Wicky, David K Bilkey, Stephanie M Hughes, Dorothy E Oorschot

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Steve SeoDepartment of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
Louise C Parr-BrownlieDepartment of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
Hollie E WickyBrain Health Research Centre, University of Otago, Dunedin 9054, New Zealand.
David K BilkeyBrain Health Research Centre, University of Otago, Dunedin 9054, New Zealand.ORCID 0000-0002-1256-4888
Stephanie M HughesBrain Health Research Centre, University of Otago, Dunedin 9054, New Zealand.ORCID 0000-0002-7142-0040
Dorothy E OorschotDepartment of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.ORCID 0000-0003-0212-4456

Funding

Neurological Foundation of New Zealand 1625 PG
6 · The paper itself

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. However, the core biology of the disorder that leads to the hypofunctioning of the cerebral dopaminergic network requires further elucidation. We investigated midbrain synaptic changes in male rats exposed to repeated hypoxia during the equivalent of extreme prematurity, which is a new animal model of the hyperactive/impulsive presentation of ADHD. We used a novel combination of a lentiviral vector, peroxidase-immunonanogold double-labelling, three-dimensional serial section transmission electron microscopy and stereological techniques to investigate the synapses formed between GABAergic axons of the rostromedial tegmental nucleus (RMTg) and dopaminergic neurons of the posterior ventral tegmental area (pVTA). This is a key site that sends extensive dopaminergic projections to the forebrain. We also compared the results to our previous study on a schizophrenia risk factor that produces cerebral hyperdopaminergia. In total, 117 reconstructed synapses were compared. Repeated hypoxic rats had a significantly thicker (22%) and longer (18%) postsynaptic density at RMTg GABAergic-pVTA dopaminergic synapses compared to their controls. These results were opposite to those previously observed in rats exposed to a schizophrenia risk factor. These findings for repeated hypoxic rats suggest that the enhanced inhibition of pVTA dopaminergic neurons may contribute to hypodopaminergia in ADHD motor hyperactivity. Synaptic triads, a key component of pVTA circuitry, were not detected in repeated hypoxic rats, indicating a marked deficit. The current knowledge may guide development in males of novel, site-specific ADHD drugs, which is necessary due to the rising prevalence of ADHD, the chronic nature of ADHD symptoms and the limitations of the currently available medications.

Indexed as

Attention Deficit Disorder with HyperactivityDopaminergic NeuronsGABAergic NeuronsSynapsesVentral Tegmental AreaAnimalsDisease Models, AnimalHypoxiaMaleRatsRats, Sprague-DawleyRisk Factorsdopaminergic posterior ventral tegmental neuronsimmunonanogoldrostromedial tegmental GABAergic neuronsschizophreniaserial section transmission electron microscopystereology

Identifiers

PMID39684680
PMCPMC11640787

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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.