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Title: Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.
Authors: Cippitelli, Andrea
Astarita, Giuseppe
Duranti, Andrea
Caprioli, Giovanni
Ubaldi, Massimo
Stopponi, Serena
Kallupi, Marsida
Sagratini, Gianni
Rodríguez de Fonseca, Fernando
Piomelli, Daniele
Ciccocioppo, Roberto
metadata.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.
Keywords: Enfermedad aguda;Amidohidrolasas;Animales;Ansiedad;Ácidos araquidónicos;Benzamidas;Encéfalo;Carbamatos;Cotinina;Endocanabinoides;Glicéridos;Implantes experimentales;Locomoción;Masculino;Aprendizaje por laberinto;Nicotina;Alcamidas poliinsaturadas;Ratas;Síndrome de abstinencia a sustancias;Productos para dejar de fumar tabaco;Aumento de peso
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Emotions::Anxiety
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Arachidonic Acids
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Benzamides
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Carbamates
Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrrolidines::Pyrrolidinones::Cotinine
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids
Medical Subject Headings::Chemicals and Drugs::Lipids::Glycerides
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Prostheses and Implants::Implants, Experimental
Medical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Locomotion
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Maze Learning
Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Alkaloids::Solanaceous Alkaloids::Nicotine
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Polyunsaturated Alkamides
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, Wistar
Medical Subject Headings::Diseases::Substance-Related Disorders::Substance Withdrawal Syndrome
Medical Subject Headings::Technology, Industry, Agriculture::Technology, Industry, and Agriculture::Manufactured Materials::Tobacco Use Cessation Products
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Growth::Body Size::Body Weight::Body Weight Changes::Weight Gain
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Acute Disease
Issue Date: 30-Nov-2011
Publisher: Public Library of Science
Citation: Cippitelli A, Astarita G, Duranti A, Caprioli G, Ubaldi M, Stopponi S, et al. Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition. PLoS ONE.2011; 6(11):e28142
Abstract: Evidence 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.
Description: Journal Article; Research Support, Non-U.S. Gov't;
metadata.dc.identifier.doi: 10.1371/journal.pone.0028142
Appears in Collections:Instituto de Investigación Biomédica de Málaga - Plataforma Bionand (IBIMA)
SAS - Hospital Universitario Regional de Málaga

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