Evidence map›Paper›PMID 37930965›Full record

ArticlePloS one2023

Dorsal raphe stimulation relays a reward signal to the ventral tegmental area via GluN2C NMDA receptors.

Giovanni Hernandez, Willemieke M Kouwenhoven, Emmanuelle Poirier, Karim Lebied, Daniel Lévesque, Pierre-Paul Rompré

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.1field-weighted citation impact, top 51% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Review
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 at 1 institution in 1 country.

Giovanni HernandezDépartement de Neurosciences (Faculté de Médecine), Université de Montréal, Montréal, QC, Canada.
Willemieke M KouwenhovenDépartement de Pharmacologie et Physiologie (Faculté de Médecine), Université de Montréal, Montréal, QC, Canada.
Emmanuelle PoirierDépartement de Neurosciences (Faculté de Médecine), Université de Montréal, Montréal, QC, Canada.
Karim LebiedDépartement de Neurosciences (Faculté de Médecine), Université de Montréal, Montréal, QC, Canada.
Daniel LévesqueDépartement de Pharmacie (Faculté de Pharmacie), Université de Montréal, Montréal, QC, Canada.ORCID 0000-0002-3019-3048
Pierre-Paul RompréDépartement de Neurosciences (Faculté de Médecine), Université de Montréal, Montréal, QC, Canada.
Université de Montréal · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlutamate relays a reward signal from the dorsal raphe (DR) to the ventral tegmental area (VTA). However, the role of the different subtypes of N-methyl-D-aspartate (NMDA) receptors is complex and not clearly understood. Therefore, we measured NMDA receptors subunits expression in limbic brain areas. In addition, we studied the effects of VTA down-regulation of GluN2C NMDA receptor on the reward signal that arises from DR electrical stimulation.

methodsUsing qPCR, we identified the relative composition of the different Grin2a-d subunits of the NMDA receptors in several brain areas. Then, we used fluorescent in situ hybridization (FISH) to evaluate the colocalization of Grin2c and tyrosine hydroxylase (TH) mRNA in VTA neurons. To assess the role of GluN2C in brain stimulation reward, we downregulated this receptor using small interfering RNA (siRNA) in rats self-stimulating for electrical pulses delivered to the DR. To delineate further the specific role of GluN2C in relaying the reward signal, we pharmacologically altered the function of VTA NMDA receptors by bilaterally microinjecting the NMDA receptor antagonist PPPA.

resultsWe identified GluN2C as the most abundant subunit of the NMDA receptor expressed in the VTA. FISH revealed that about 50% of TH-positive neurons colocalize with Grin2c transcript. siRNA manipulation produced a selective down-regulation of the GluN2C protein subunit and a significant reduction in brain stimulation reward. Interestingly, PPPA enhanced brain stimulation reward, but only in rats that received the nonactive RNA sequence.

conclusionThe present results suggest that VTA glutamate neurotransmission relays a reward signal initiated by DR stimulation by acting on GluN2C NMDA receptors.

Indexed as

Dorsal Raphe NucleusReceptors, N-Methyl-D-AspartateAnimalsGlutamic AcidIn Situ Hybridization, FluorescenceRatsRewardRNA, Small InterferingVentral Tegmental AreaGlutamic AcidReceptors, N-Methyl-D-AspartateRNA, Small Interfering

Identifiers

PMID37930965
PMCPMC10627466
OpenAlexW4388408280

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.