Evidence map›Paper›PMID 28209735›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2017

The Epac-Phospholipase Cε Pathway Regulates Endocannabinoid Signaling and Cocaine-Induced Disinhibition of Ventral Tegmental Area Dopamine Neurons.

Jiaqing Tong, Xiaojie Liu, Casey Vickstrom, Yan Li, Laikang Yu, Youming Lu, Alan V Smrcka, Qing-Song Liu

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Role of mesolimbic cannabinoid receptor 1 in stress-driven increases in cocaine self-administration in male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 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

8 authors at 3 institutions in 2 countries.

Jiaqing TongDepartment of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.ORCID 0000-0002-2587-0251
Xiaojie LiuDepartment of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.ORCID 0000-0001-9843-1674
Casey VickstromDepartment of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.ORCID 0000-0003-0536-1211
Yan LiDepartment of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.
Laikang YuDepartment of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.
Youming LuNeuroscience Center of Excellence and Department of Neurology, Louisiana State University School of Medicine, New Orleans, Louisiana 70112.
Alan V SmrckaDepartment of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
Qing-Song LiuDepartment of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, qsliu@mcw.edu.ORCID 0000-0003-1858-1504
Medical College of Wisconsin · USLouisiana State University · USUniversity of Michigan · US

Funding

Medical Scientist Training ProgramT32GM080202 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI BARBIERI, JOSEPH T, SALZMAN, NITA H · 2010 to 2024
$5.7M
SIGNAL TRANSDUCTION BY G PROTEINR01GM053536 · NIGMS · UNIVERSITY OF ROCHESTER · PI SMRCKA, ALAN V. · 1996 to 2018
$4.9M
Mechanistic studies of phosphodiesterase inhibitors in cocaine addictionR01DA035217 · NIDA · MEDICAL COLLEGE OF WISCONSIN · PI LIU, QING-SONG · 2014 to 2023
$3.4M
Regulation of dopamine neuronal activity and depressive behavior by HCN channelsR56MH101146 · NIMH · MEDICAL COLLEGE OF WISCONSIN · PI LIU, QING-SONG · 2014 to 2015
$765k
NIDA NIH HHS R01 DA035217NIGMS NIH HHS R01 GM053536NIGMS NIH HHS T32 GM080202NIMH NIH HHS R56 MH101146
6 · The paper itself

Abstract

Exchange protein directly activated by cAMP (Epac) is a direct effector for the ubiquitous second messenger cAMP. Epac activates the phospholipase Cε (PLCε) pathway. PLCβ has been linked to the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Here, we report that Epac facilitates endocannabinoid-mediated retrograde synaptic depression through activation of PLCε. Intracellular loading of a selective Epac agonist 8-CPT-2Me-cAMP into ventral tegmental area (VTA) dopamine neurons enabled previously ineffective stimuli to induce depolarization-induced suppression of inhibition (DSI) and long-term depression of IPSCs (I-LTD) in the VTA. DSI and I-LTD are mediated by 2-AG since they were blocked by a diacylglycerol lipase inhibitor. The effects of 8-CPT-2Me-cAMP on DSI and I-LTD were absent in Epac2 and PLCε knock-out mice, but remained intact in Epac1 knock-out mice. These results identify a novel mechanism for on-demand synthesis of retrograde signaling 2-AG by the Epac2-PLCε pathway. We investigated the functional significance of Epac2-PLCε-2-AG signaling in regulating inhibitory synaptic plasticity in VTA dopamine neurons induced by

Indexed as

AnimalsCocaineDopaminergic NeuronsEndocannabinoidsFemaleMaleMiceMice, Inbred C57BLMice, KnockoutNeural InhibitionPhosphoinositide Phospholipase CSignal TransductionVentral Tegmental AreaCocaineEndocannabinoidsPhosphoinositide Phospholipase Cphospholipase C epsilonendocannabinoid 2-arachidonoylglycerolEpacGABAergic disinhibitionphospholipase Cεretrograde synaptic depression

Identifiers

PMID28209735
PMCPMC5354337
OpenAlexW2588212808

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.