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Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.

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dc.contributor.authorCippitelli, Andrea
dc.contributor.authorAstarita, Giuseppe
dc.contributor.authorDuranti, Andrea
dc.contributor.authorCaprioli, Giovanni
dc.contributor.authorUbaldi, Massimo
dc.contributor.authorStopponi, Serena
dc.contributor.authorKallupi, Marsida
dc.contributor.authorSagratini, Gianni
dc.contributor.authorRodríguez de Fonseca, Fernando
dc.contributor.authorPiomelli, Daniele
dc.contributor.authorCiccocioppo, Roberto
dc.contributor.authoraffiliation[Cippitelli,A; Ubaldi,M; Stopponi,S; Kallupi,M; Ciccocioppo,R] School of Pharmacy,Pharmacology Unit,University of Camerino,Camerino,Italy. [Astarita,G; Piomelli,D] Department of Pharmacology, University of California Irvine, Irvine, California, United States of America. [Duranti,A] Department of Biomolecular Sciences, Medicinal Chemistry and Technology Unit, University of Urbino ‘‘Carlo Bo’’, Urbino, Italy. [Caprioli,G; Sagratini,G] School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Camerino,Italy. [Rodríguez de Fonseca,F] Fundación IMABIS, Hospital Carlos Haya de Málaga, Málaga, Spain. [Piomelli,D] Drug Discovery and Development, Italian Institute of Technology, Genova, Italy.
dc.date.accessioned2024-01-15T18:16:44Z
dc.date.available2024-01-15T18:16:44Z
dc.date.issued2011-11-30
dc.description.abstractEvidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use.
dc.description.sponsorshipUniversity of Camerino, Italy
dc.identifier.doi10.1371/journal.pone.0028142
dc.identifier.e-issn1932-6203es_ES
dc.identifier.journalPloS ONEes_ES
dc.identifier.otherhttp://hdl.handle.net/10668/704
dc.identifier.pubmedID22140525es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/17034
dc.language.isoeng
dc.publisherPublic Library of Science (PLOS)
dc.relation.publisherversionhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0028142es
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectEnfermedad aguda
dc.subjectAmidohidrolasas
dc.subjectAnimales
dc.subjectAnsiedad
dc.subjectÁcidos araquidónicos
dc.subjectBenzamidas
dc.subjectEncéfalo
dc.subjectCarbamatos
dc.subjectCotinina
dc.subjectEndocanabinoides
dc.subjectGlicéridos
dc.subjectImplantes experimentales
dc.subjectLocomoción
dc.subjectMasculino
dc.subjectAprendizaje por laberinto
dc.subjectNicotina
dc.subjectAlcamidas poliinsaturadas
dc.subjectRatas
dc.subjectSíndrome de abstinencia a sustancias
dc.subjectProductos para dejar de fumar tabaco
dc.subjectAumento de peso
dc.subject.meshAmidohydrolases
dc.subject.meshAnimals
dc.subject.meshAnxiety
dc.subject.meshArachidonic Acids
dc.subject.meshBenzamides
dc.subject.meshBrain
dc.subject.meshCarbamates
dc.subject.meshCotinine
dc.subject.meshEndocannabinoids
dc.subject.meshGlycerides
dc.subject.meshImplants, Experimental
dc.subject.meshMovement
dc.subject.meshMale
dc.subject.meshMaze Learning
dc.subject.meshNicotine
dc.subject.meshPolyunsaturated Alkamides
dc.subject.meshRats
dc.subject.meshRats, Wistar
dc.subject.meshSubstance Withdrawal Syndrome
dc.subject.meshTobacco Use Cessation Products
dc.subject.meshWeight Gain
dc.subject.meshAcute Disease
dc.titleEndocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication
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