title: Chronic stimulation of the tone of endogenous anandamide reduces cue- and stress-induced relapse in rats.
abstract: BACKGROUND
  The endogenous cannabinoid system plays an important role in motivation, stress, and drug abuse. Pharmacologically, the endocannabinoid system can be stimulated by either agonists of CB1 receptors or inhibition of metabolic degradation of endogenous cannabinoids and consequent increases in their brain levels.
  
  
  METHODS
  Here, we investigated whether chronic administration during a period of withdrawal of the fatty acid amide hydrolase inhibitor URB597, which increases anandamide levels, would decrease the risks of relapse to cocaine seeking. Rats were allowed to self-administer cocaine and then they underwent forced withdrawal for 28 days, during which they were treated with URB597 or vehicle. One day after the last injection, we investigated cocaine seeking in one 6h extinction session and relapse triggered by re-exposure to drug-associated cues or a pharmacological stressor.
  
  
  RESULTS
  We found that administration of URB597 significantly decreases cocaine-seeking behavior and cue- and stress-induced relapse.
  
  
  CONCLUSIONS
  These results suggest that stimulation of the endocannabinoid system could be helpful to prevent relapse to cocaine addiction.
authors.affiliation: University of Poitiers, France (Drs Chauvet, Nicolas, Thiriet, Lardeux, and Solinas); INSERM, Experimental and Clinical Neurosciences Laboratory, Poitiers, FRANCE (Drs Nicolas, Thiriet, Lardeux, and Solinas); Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo," Urbino, Italy (Dr Duranti).
authors.forename: Claudia
authors.initials: C
authors.lastname: Chauvet
authors.affiliation: University of Poitiers, France (Drs Chauvet, Nicolas, Thiriet, Lardeux, and Solinas); INSERM, Experimental and Clinical Neurosciences Laboratory, Poitiers, FRANCE (Drs Nicolas, Thiriet, Lardeux, and Solinas); Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo," Urbino, Italy (Dr Duranti).
authors.forename: Céline
authors.initials: C
authors.lastname: Nicolas
authors.affiliation: University of Poitiers, France (Drs Chauvet, Nicolas, Thiriet, Lardeux, and Solinas); INSERM, Experimental and Clinical Neurosciences Laboratory, Poitiers, FRANCE (Drs Nicolas, Thiriet, Lardeux, and Solinas); Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo," Urbino, Italy (Dr Duranti).
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thiriet
authors.affiliation: University of Poitiers, France (Drs Chauvet, Nicolas, Thiriet, Lardeux, and Solinas); INSERM, Experimental and Clinical Neurosciences Laboratory, Poitiers, FRANCE (Drs Nicolas, Thiriet, Lardeux, and Solinas); Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo," Urbino, Italy (Dr Duranti).
authors.forename: Md Virginie
authors.initials: MV
authors.lastname: Lardeux
authors.affiliation: University of Poitiers, France (Drs Chauvet, Nicolas, Thiriet, Lardeux, and Solinas); INSERM, Experimental and Clinical Neurosciences Laboratory, Poitiers, FRANCE (Drs Nicolas, Thiriet, Lardeux, and Solinas); Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo," Urbino, Italy (Dr Duranti).
authors.forename: Andrea
authors.initials: A
authors.lastname: Duranti
authors.affiliation: University of Poitiers, France (Drs Chauvet, Nicolas, Thiriet, Lardeux, and Solinas); INSERM, Experimental and Clinical Neurosciences Laboratory, Poitiers, FRANCE (Drs Nicolas, Thiriet, Lardeux, and Solinas); Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo," Urbino, Italy (Dr Duranti). marcello.solinas@univ-poitiers.fr.
authors.forename: Marcello
authors.initials: M
authors.lastname: Solinas
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001549:Benzamides / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003463:Cues; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology*; D063388:Endocannabinoids / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012646:Self Administration; D013312:Stress, Physiological / Q000502:physiology*; D015016:Yohimbine; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D001549:Benzamides; D002219:Carbamates; D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D053284:Polyunsaturated Alkamides; D015016:Yohimbine; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C078814:anandamide
keywords: FAAH; abstinence; addiction; chronic treatment; endocannabinoid; psychostimulants; relapse; stress