RT Journal Article
T1 Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.
A1 Cippitelli, Andrea
A1 Astarita, Giuseppe
A1 Duranti, Andrea
A1 Caprioli, Giovanni
A1 Ubaldi, Massimo
A1 Stopponi, Serena
A1 Kallupi, Marsida
A1 Sagratini, Gianni
A1 Rodríguez de Fonseca, Fernando
A1 Piomelli, Daniele
A1 Ciccocioppo, Roberto
K1 Enfermedad aguda
K1 Amidohidrolasas
K1 Animales
K1 Ansiedad
K1 Ácidos araquidónicos
K1 Benzamidas
K1 Encéfalo
K1 Carbamatos
K1 Cotinina
K1 Endocanabinoides
K1 Glicéridos
K1 Implantes experimentales
K1 Locomoción
K1 Masculino
K1 Aprendizaje por laberinto
K1 Nicotina
K1 Alcamidas poliinsaturadas
K1 Ratas
K1 Síndrome de abstinencia a sustancias
K1 Productos para dejar de fumar tabaco
K1 Aumento de peso
AB 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.
PB Public Library of Science
YR 2011
FD 2011-11-30
LK http://hdl.handle.net/10668/704
UL http://hdl.handle.net/10668/704
LA en
NO 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
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 8, 2025