| The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition. | |
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MedLine Citation:
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PMID: 17904589 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Converging evidence suggests that the endocannabinoid system is an important constituent of neuronal substrates involved in brain reward processes and emotional responses to stress. Here, we evaluated motivational effects of intravenously administered anandamide, an endogenous ligand for cannabinoid CB1-receptors, in Sprague-Dawley rats, using a place-conditioning procedure in which drugs abused by humans generally produce conditioned place preferences (reward). Anandamide (0.03-3 mg/kg intravenous) produced neither conditioned place preferences nor aversions. However, when rats were pre-treated with the fatty acid amide hydrolase (FAAH) inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester; 0.3 mg/kg intraperitoneal), which blocks anandamide's metabolic degradation, anandamide produced dose-related conditioned place aversions. In contrast, URB597 alone showed no motivational effects. Like URB597 plus anandamide, the synthetic CB1-receptor ligand WIN 55,212-2 (50-300 microg/kg, intravenous) produced dose-related conditioned place aversions. When anxiety-related effects of anandamide and URB597 were evaluated in a light/dark box, both a low anandamide dose (0.3 mg/kg) and URB597 (0.1 and 0.3 mg/kg) produced anxiolytic effects when given alone, but produced anxiogenic effects when combined. A higher dose of anandamide (3 mg/kg) produced anxiogenic effects and depressed locomotor activity when given alone and these effects were potentiated after URB597 treatment. Finally, anxiogenic effects of anandamide plus URB597 and development of place aversions with URB597 plus anandamide were prevented by the CB1-receptor antagonist AM251 (3 mg/kg intraperitoneal). Thus, additive interactions between the effects of anandamide on brain reward processes and on anxiety may account for its aversive effects when intravenously administered during FAAH inhibition with URB597. |
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Authors:
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Maria Scherma; Julie Medalie; Walter Fratta; Subramanian K Vadivel; Alexandros Makriyannis; Daniele Piomelli; Eva Mikics; Jozsef Haller; Sevil Yasar; Gianluigi Tanda; Steven R Goldberg |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-08-19 |
Journal Detail:
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Title: Neuropharmacology Volume: 54 ISSN: 0028-3908 ISO Abbreviation: Neuropharmacology Publication Date: 2008 Jan |
Date Detail:
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Created Date: 2007-12-31 Completed Date: 2008-04-18 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0236217 Medline TA: Neuropharmacology Country: England |
Other Details:
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Languages: eng Pagination: 129-40 Citation Subset: IM |
Affiliation:
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Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amidohydrolases
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metabolism* Analgesics / pharmacology Analysis of Variance Animals Anxiety / drug therapy, enzymology* Arachidonic Acids / metabolism*, pharmacology Avoidance Learning / drug effects Behavior, Animal / drug effects Benzamides / pharmacology Benzoxazines / pharmacology Carbamates / pharmacology Conditioning, Operant / drug effects Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Male Morpholines / pharmacology Motivation* Motor Activity / drug effects Naphthalenes / pharmacology Polyunsaturated Alkamides / metabolism*, pharmacology Rats Rats, Sprague-Dawley Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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DA09158/DA/NIDA NIH HHS; DA12413/DA/NIDA NIH HHS; DA12447/DA/NIDA NIH HHS; DA7215/DA/NIDA NIH HHS; Z01 DA000001-23/DA/NIDA NIH HHS; Z01 DA000003-22/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Analgesics; 0/Arachidonic Acids; 0/Benzamides; 0/Benzoxazines; 0/Carbamates; 0/Enzyme Inhibitors; 0/Morpholines; 0/Naphthalenes; 0/Polyunsaturated Alkamides; 0/cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; 134959-51-6/Win 55212-2; 94421-68-8/anandamide; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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