Evidence map›Paper›PMID 26803499›Full record

ArticlePsychopharmacology2016

Self-administration of the anandamide transport inhibitor AM404 by squirrel monkeys.

Charles W Schindler, Maria Scherma, Godfrey H Redhi, Subramanian K Vadivel, Alexandros Makriyannis, Steven R Goldberg, Zuzana Justinova

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

Article in Psychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.7field-weighted citation impact, top 8% 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

8 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Endocannabinoid Regulation of Reward and Reinforcement through Interaction with Dopamine and Endogenous Opioid Signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018
    Review
  5. Preclinical Studies of Cannabinoid Reward, Treatments for Cannabis Use Disorder, and Addiction-Related Effects of Cannabinoid Exposure.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018
    Review
  6. Review
  7. Review
  8. Article
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

7 authors at 4 institutions in 2 countries.

Charles W SchindlerPreclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 251 Bayview Boulevard, Baltimore, MD, 21224, USA. cschind@helix.nih.gov.
Maria SchermaDepartment of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Monserrato, Italy.
Godfrey H RedhiPreclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
Subramanian K VadivelCenter for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.
Alexandros MakriyannisCenter for Drug Discovery, Departments of Pharmaceutical Sciences and Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
Steven R GoldbergPreclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
Zuzana JustinovaPreclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
National Institutes of Health · USNortheastern University · USNational Institute on Drug Abuse · USUniversity of Cagliari · IT

Funding

Project 3 - In vivo pharmacology of cannabinoid receptor probesP01DA009158 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI Alexandros Makriyannis · 1994 to 2026
$26.0M
Control Of Behavior By Drug InjectionsZIADA000001 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI SHAHAM, YAVIN · 2009 to 2016
$8.3M
CANNABINOID LIGANDS AND DRUGSR01DA007215 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI MAKRIYANNIS, ALEXANDROS · 1993 to 2012
$3.6M
MOLECULAR BASIS OF CANNABINOID ACTIVITYR01DA003801 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI MAKRIYANNIS, ALEXANDROS · 1985 to 2017
$2.5M
Intramural NIH HHS ZIA DA000001NIDA NIH HHS P01 DA009158NIDA NIH HHS R01 DA003801NIDA NIH HHS R01 DA007215
6 · The paper itself

Abstract

rationaleN-(4-hydroxyphenyl)-arachidonamide (AM404) is an anandamide transport inhibitor shown to reduce rewarding and relapse-inducing effects of nicotine in several animal models of tobacco dependence. However, the reinforcing/rewarding effects of AM404 are not clear.

objectivesWe investigated whether AM404 maintains self-administration behavior or reinstates extinguished drug seeking in squirrel monkeys. METHODS AND

resultsIn monkeys with a history of anandamide or cocaine self-administration, we substituted injections of AM404 (1-100 μg/kg/injection). Using a 10-response, fixed-ratio schedule, self-administration behavior was maintained by AM404. Dose-response curves had inverted U shapes, with peak response rates occurring at a dose of 10 μg/kg/injection. In anandamide-experienced monkeys, we also demonstrated self-administration of another anandamide transport inhibitor VDM11. In addition to supporting self-administration, priming injections of AM404 (0.03-0.3 mg/kg) reinstated drug-seeking behavior previously reinforced by cannabinoids (∆(9)-tetrahydrocannabinol (THC) or anandamide) or cocaine. Both AM404 self-administration behavior and reinstatement of drug seeking by AM404 were reduced by treatment with the cannabinoid CB1 receptor antagonist/inverse agonist rimonabant (0.3 mg/kg). Moreover, the reinforcing effects of AM404 were potentiated by the treatment with the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg) suggesting a major role of anandamide in these effects. Finally, AM404 (0.3 mg/kg) potentiated the reinforcing effects of anandamide but not those of cocaine.

conclusionsIn non-human primates, AM404 effectively reinforced self-administration behavior and induced reinstatement of drug-seeking behavior in abstinent monkeys. These effects appeared to be mediated by cannabinoid CB1 receptors. Therefore, compounds that promote actions of endocannabinoids throughout the brain by inhibiting their membrane transport may have a potential for abuse.

Indexed as

AnimalsArachidonic AcidsBenzamidesCannabinoid Receptor AntagonistsCarbamatesCocaineDose-Response Relationship, DrugDronabinolDrug-Seeking BehaviorEndocannabinoidsMaleNicotinePiperidinesPolyunsaturated AlkamidesPyrazolesReinforcement, PsychologyanandamideArachidonic AcidsBenzamidesCannabinoid Receptor AntagonistsCarbamatesCocainecyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl esterDronabinolEndocannabinoidsN-(2-methyl-3-hydroxyphenyl)-5,8,11,14-eicosatetraenamideN-(4-hydroxyphenyl)arachidonylamideNicotinePiperidinesPolyunsaturated AlkamidesPyrazolesRimonabantAM404AnandamideReinstatementRimonabantSelf-administrationSquirrel monkeys

Identifiers

PMID26803499
PMCPMC4846479
OpenAlexW2293299740

What OpenQuestion holds

Textmetadata
LicenceTDM
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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.