651. Endocannabinoid Regulation of Acute and Protracted Nicotine Withdrawal: Effect of FAAH Inhibition
- Author
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Giuseppe Astarita, Gianni Sagratini, Andrea Cippitelli, Giovanni Caprioli, Serena Stopponi, Fernando Rodríguez de Fonseca, Massimo Ubaldi, Andrea Duranti, Daniele Piomelli, Marsida Kallupi, Roberto Ciccocioppo, [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., and University of Camerino, Italy
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Productos para dejar de fumar tabaco ,Male ,Amidohidrolasas ,Carbamatos ,Anxiety ,Pharmacology ,Weight Gain ,Biochemistry ,Behavioral Neuroscience ,Implants, Experimental ,Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Carbamates [Medical Subject Headings] ,Fatty acid amide hydrolase ,Organisms::Eukaryota::Animals [Medical Subject Headings] ,Cotinina ,Masculino ,lcsh:Science ,Cotinine ,Aprendizaje por laberinto ,Life Sciences ,Brain ,Benzamidas ,Neurotransmitters ,Anandamide ,Tobacco Use Cessation Devices ,Nicotine withdrawal ,Acute Disease ,Medicine ,Locomotion ,Nicotine ,Elevated plus maze ,Polyunsaturated Alkamides ,Nicotina ,Aumento de peso ,Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Maze Learning [Medical Subject Headings] ,Check Tags::Male [Medical Subject Headings] ,Glycerides ,Technology, Industry, Agriculture::Technology, Industry, and Agriculture::Manufactured Materials::Tobacco Use Cessation Products [Medical Subject Headings] ,Ansiedad ,Síndrome de abstinencia a sustancias ,Locomoción ,Cannabinoid Receptor Modulators ,Ácidos araquidónicos ,Rats, Wistar ,Psychiatry and Psychology::Behavior and Behavior Mechanisms::Emotions::Anxiety [Medical Subject Headings] ,Maze Learning ,smoking-cessation ,Biology ,Endocanabinoides ,lcsh:R ,medicine.disease ,Nicotine replacement therapy ,Chemicals and Drugs::Organic Chemicals::Amides::Polyunsaturated Alkamides [Medical Subject Headings] ,Chemicals and Drugs::Lipids::Glycerides [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings] ,chemistry ,Animales ,Rat ,lcsh:Q ,Carbamates ,Chemicals and Drugs::Organic Chemicals::Amides::Benzamides [Medical Subject Headings] ,Neuroscience ,Psychopharmacology ,Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Growth::Body Size::Body Weight::Body Weight Changes::Weight Gain [Medical Subject Headings] ,lcsh:Medicine ,chemistry.chemical_compound ,elevated plus-maze ,Medicine and Health Sciences ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, Wistar [Medical Subject Headings] ,restraint stress ,Implantes experimentales ,Multidisciplinary ,brain reward function ,anxiety-like behavior ,Enfermedad aguda ,abstinence syndrome ,corticotropin-releasing factor ,Neurochemistry ,Animal Models ,Endocannabinoid system ,Substance Withdrawal Syndrome ,Alcamidas poliinsaturadas ,Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrrolidines::Pyrrolidinones::Cotinine [Medical Subject Headings] ,Encéfalo ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Prostheses and Implants::Implants, Experimental [Medical Subject Headings] ,Behavioral Pharmacology ,Benzamides ,Diseases::Substance-Related Disorders::Substance Withdrawal Syndrome [Medical Subject Headings] ,lipids (amino acids, peptides, and proteins) ,Neurochemicals ,Chemicals and Drugs::Heterocyclic Compounds::Alkaloids::Solanaceous Alkaloids::Nicotine [Medical Subject Headings] ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Arachidonic Acids [Medical Subject Headings] ,cannabinoid system ,Research Article ,medicine.drug ,Drugs and Devices ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Acute Disease [Medical Subject Headings] ,Arachidonic Acids ,Amidohydrolases ,Ratas ,Model Organisms ,medicine ,Animals ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids [Medical Subject Headings] ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases [Medical Subject Headings] ,Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings] ,URB597 ,Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Locomotion [Medical Subject Headings] ,Rats ,locomotor-activity ,amide hydrolase faah ,Glicéridos ,Endocannabinoids - Abstract
Journal Article; Research Support, Non-U.S. Gov't; 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. Yes
- Published
- 2011