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00925njm 22002777a 4500 dc Cippitelli, Andrea author Astarita, Giuseppe author Duranti, Andrea author Caprioli, Giovanni author Ubaldi, Massimo author Stopponi, Serena author Kallupi, Marsida author Sagratini, Gianni author Rodríguez de Fonseca, Fernando author Piomelli, Daniele author Ciccocioppo, Roberto author 2011-11-30 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. 10.1371/journal.pone.0028142 1932-6203 PloS ONE http://hdl.handle.net/10668/704 22140525 http://hdl.handle.net/20.500.12105/18883 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 Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition