Endocannabinoid Regulation of Acute and Protracted Nicotine Withdrawal: Effect of FAAH Inhibition

摘要: Evidence shows that the endocannabinoid system modulates addictive properties of nicotine. In present study, we hypothesized spontaneous withdrawal resulting from removal chronically implanted transdermal nicotine patches is regulated by system. A 7-day dependence procedure (5.2 mg/rat/day) elicited occurrence reliable abstinence symptoms in Wistar rats. Somatic and affective signs were observed at 16 34 hours following patches, respectively. Further behavioral manifestations including decrease locomotor activity increased weight gain also occurred during withdrawal. Expression was accompanied fluctuation levels anandamide (AEA) several brain structures amygdala, hippocampus, hypothalamus prefrontal cortex. Conversely, 2-arachidonoyl-sn-glycerol not significantly altered. Pharmacological inhibition fatty acid amide hydrolase (FAAH), enzyme responsible for intracellular degradation AEA, URB597 (0.1 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed elevated plus maze test shock-probe defensive burying paradigm, but did prevent somatic signs. Together, results indicate pharmacological strategies aimed enhancing signaling may offer therapeutic advantages to treat negative state produced withdrawal, which critical maintenance tobacco use.