Evidence map›Paper›PMID 22860119›Full record

ArticlePloS one2012

Identification of rat ventral tegmental area GABAergic neurons.

Elyssa B Margolis, Brian Toy, Patricia Himmels, Marisela Morales, Howard L Fields

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

117 citing papers in PubMed, 208 citations in OpenAlex.

  1. Article
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  3. NAcLat-DBS reduces GABANeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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  11. Review
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  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. The Formation and Function of the VTA Dopamine System.International journal of molecular sciences · 2024
    Review
  20. Article

57 more citing papers are in PubMed but not listed here.

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 1 country.

Elyssa B MargolisErnest Gallo Clinic and Research Center, University of California San Francisco, Emeryville, California, United States of America. elyssam@gallo.ucsf.edu
Brian Toy
Patricia Himmels
Marisela Morales
Howard L Fields
Ernest Gallo Clinic and Research Center · USUniversity of California, San Francisco · USNational Institute on Drug Abuse · US

Funding

Heterogeneity of Ventral Tegmental Area Neurons and Opioid RewardR01DA030529 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARGOLIS, ELYSSA · 2011 to 2015
$1.8M
Intramural NIH HHSNIDA NIH HHS R01 DA030529NIDA NIH HHS R01DA030529
6 · The paper itself

Abstract

The canonical two neuron model of opioid reward posits that mu opioid receptor (MOR) activation produces reward by disinhibiting midbrain ventral tegmental area (VTA) dopamine neurons through inhibition of local GABAergic interneurons. Although indirect evidence supports the neural circuit postulated by this model, its validity has been called into question by growing evidence for VTA neuronal heterogeneity and the recent demonstration that MOR agonists inhibit GABAergic terminals in the VTA arising from extrinsic neurons. In addition, VTA MOR reward can be dopamine-independent. To directly test the assumption that MOR activation directly inhibits local GABAergic neurons, we investigated the properties of rat VTA GABA neurons directly identified with either immunocytochemistry for GABA or GAD65/67, or in situ hybridization for GAD65/67 mRNA. Utilizing co-labeling with an antibody for the neural marker NeuN and in situ hybridization against GAD65/67, we found that 23±3% of VTA neurons are GAD65/67(+). In contrast to the assumptions of the two neuron model, VTA GABAergic neurons are heterogeneous, both physiologically and pharmacologically. Importantly, only 7/13 confirmed VTA GABA neurons were inhibited by the MOR selective agonist DAMGO. Interestingly, all confirmed VTA GABA neurons were insensitive to the GABA(B) receptor agonist baclofen (0/6 inhibited), while all confirmed dopamine neurons were inhibited (19/19). The heterogeneity of opioid responses we found in VTA GABAergic neurons, and the fact that GABA terminals arising from neurons outside the VTA are inhibited by MOR agonists, make further studies essential to determine the local circuit mechanisms underlying VTA MOR reward.

Indexed as

Animalsgamma-Aminobutyric AcidImmunohistochemistryNeuronsRatsVentral Tegmental Areagamma-Aminobutyric Acid

Identifiers

PMID22860119
PMCPMC3409171
OpenAlexW1977934441

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.