Evidence map›Paper›PMID 24061495›Full record

ArticleMolecular psychiatry2014

Antidepressant-like and anxiolytic-like effects following activation of the μ-δ opioid receptor heteromer in the nucleus accumbens.

N Kabli, T Nguyen, G Balboni, B F O'Dowd, S R George

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

23 citing papers in PubMed, 53 citations in OpenAlex.

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  13. Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016
    Review
  14. Article
  15. Article
  16. G Protein-Coupled Receptor Heteromers.Annual review of pharmacology and toxicology · 2016
    Review
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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

5 authors at 3 institutions in 2 countries.

N Kabli1] Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada [2] Departments of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
T NguyenCampbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada.
G BalboniDepartment of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
B F O'Dowd1] Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada [2] Departments of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
S R George1] Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, ON, Canada [2] Departments of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada [3] Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Centre for Addiction and Mental Health · CAUniversity of Cagliari · ITUniversity of Toronto · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Treatment-resistant major depressive disorder remains inadequately treated with currently available antidepressants. Opioid receptors (ORs) are involved in the pathophysiology of depression yet remain an untapped therapeutic intervention. The μ-δ OR heteromer represents a unique signaling complex with distinct properties compared with μ- and δ-OR homomers; however, its role in depression has not been characterized. As there are no ligands exclusively targeting the μ-δ heteromer, we devised a strategy to selectively antagonize the function of the μ-δOR complex using a specific interfering peptide derived from the δOR distal carboxyl tail, a sequence implicated in μ-δOR heteromerization. In vitro studies using a minigene expressing this peptide demonstrated a loss of the unique pharmacological and trafficking properties of δ-agonists at the μ-δ heteromer, with no effect on μ- or δ-OR homomers, and a dissociation of the μ-δOR complex. Intra-accumbens administration of the TAT-conjugated interfering peptide abolished the antidepressant-like and anxiolytic-like actions of the δ-agonist UFP-512 (H-Dmt-Tic-NH-CH(CH2-COOH)-Bid) measured in the forced swim test, novelty-induced hypophagia and elevated plus maze paradigms in rats. UFP-512's antidepressant-like and anxiolytic-like actions were abolished by pretreatment with either μOR or δOR antagonists. Overall, these findings demonstrate that the μ-δ heteromer may be a potential suitable therapeutic target for treatment-resistant depression and anxiety disorders.

Indexed as

AnimalsAnti-Anxiety AgentsAntidepressive AgentsAnxietyBenzimidazolesCell MembraneDepressionHEK293 CellsHumansMaleNarcotic AntagonistsNucleus AccumbensOligopeptidesRats, Sprague-DawleyReceptors, Opioid, deltaReceptors, Opioid, mu2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1H-benzimidazol-2-yl)(carboxymethyl)methylamideAnti-Anxiety AgentsAntidepressive AgentsBenzimidazolesNarcotic AntagonistsOligopeptidesReceptors, Opioid, deltaReceptors, Opioid, mu

Identifiers

PMID24061495
OpenAlexW1969179176

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.