Evidence map›Paper›PMID 25374096›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015

Species differences in cannabinoid receptor 2 and receptor responses to cocaine self-administration in mice and rats.

Hai-Ying Zhang, Guo-Hua Bi, Xia Li, Jie Li, Hong Qu, Shi-Jian Zhang, Chuan-Yun Li, Emmanuel S Onaivi, Eliot L Gardner, Zheng-Xiong Xi and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 2 pooled it
6.9field-weighted citation impact, top 3% 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

77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 127 citations in OpenAlex.

  1. Pooled it
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  8. Article
  9. The cannabinoid CBNeuropharmacology · 2025
    Article
  10. Establishing the hybrid rat diversity program: a resource for dissecting complex traits.Mammalian genome : official journal of the International Mammalian Genome Society · 2025
    Article
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17 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

11 authors at 3 institutions in 2 countries.

Hai-Ying ZhangNeuroropsychopharmacology Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Guo-Hua BiNeuroropsychopharmacology Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Xia LiNeuroropsychopharmacology Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Jie LiNeuroropsychopharmacology Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Hong QuCenter for Bioinformatics, College of Life Sciences, Peking University, Beijing, China.
Shi-Jian ZhangBeijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking University, Beijing, China.
Chuan-Yun LiBeijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking University, Beijing, China.
Emmanuel S OnaiviDepartment of Biology, William Paterson University, Wayne, NJ, USA.
Eliot L GardnerNeuroropsychopharmacology Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Zheng-Xiong XiNeuroropsychopharmacology Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
Qing-Rong LiuNeurobiology of Relapse Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.
National Institute on Drug Abuse · USPeking University · CNWilliam Paterson University · US

Funding

Basic brain mechanisms underlying drug addiction, craving, and relapseZIADA000478 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI GARDNER, ELIOT · 2009 to 2023
$7.9M
Endocannabinoid brain mechanisms and addictionZIADA000513 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI GARDNER, ELIOT · 2009 to 2020
$6.0M
BEHAVIORAL EFFECTS OF CB2 CANNABINOID RECEPTORS (CB2RS)R15DA032890 · NIDA · WILLIAM PATERSON UNIVERSITY · PI ONAIVI, EMMANUEL S · 2012 to 2012
$352k
Intramural NIH HHSNIDA NIH HHS DA032890NIDA NIH HHS R15 DA032890
6 · The paper itself

Abstract

The discovery of functional cannabinoid receptors 2 (CB2Rs) in brain suggests a potential new therapeutic target for neurological and psychiatric disorders. However, recent findings in experimental animals appear controversial. Here we report that there are significant species differences in CB2R mRNA splicing and expression, protein sequences, and receptor responses to CB2R ligands in mice and rats. Systemic administration of JWH133, a highly selective CB2R agonist, significantly and dose-dependently inhibited intravenous cocaine self-administration under a fixed ratio (FR) schedule of reinforcement in mice, but not in rats. However, under a progressive ratio (PR) schedule of reinforcement, JWH133 significantly increased breakpoint for cocaine self-administration in rats, but decreased it in mice. To explore the possible reasons for these conflicting findings, we examined CB2R gene expression and receptor structure in the brain. We found novel rat-specific CB2C and CB2D mRNA isoforms in addition to CB2A and CB2B mRNA isoforms. In situ hybridization RNAscope assays found higher levels of CB2R mRNA in different brain regions and cell types in mice than in rats. By comparing CB2R-encoding regions, we observed a premature stop codon in the mouse CB2R gene that truncated 13 amino-acid residues including a functional autophosphorylation site in the intracellular C-terminus. These findings suggest that species differences in the splicing and expression of CB2R genes and receptor structures may in part explain the different effects of CB2R-selective ligands on cocaine self-administration in mice and rats.

Indexed as

Species SpecificityAdministration, OralAnimalsBrainCannabinoidsCocaineConditioning, OperantDopamine Uptake InhibitorsMaleMiceMice, Inbred C57BLMice, KnockoutModels, MolecularRatsRats, Long-EvansReceptor, Cannabinoid, CB21,1-dimethylbutyl-1-deoxy-Delta(9)-THCCannabinoidsCnr2 protein, mouseCocaineDopamine Uptake InhibitorsReceptor, Cannabinoid, CB2SucroseSweetening Agents

Identifiers

PMID25374096
PMCPMC4330519
OpenAlexW2060231477

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.