RT Journal Article
T1 Fatty acid amide hydrolase (FAAH) inactivation confers enhanced sensitivity to nicotine-induced dopamine release in the mouse nucleus accumbens.
A1 Pavon, Francisco J
A1 Serrano, Antonia
A1 Sidhpura, Nimish
A1 Polis, Ilham
A1 Stouffer, David
A1 Rodriguez-de-Fonseca, Fernando
A1 Cravatt, Benjamin F
A1 Martin-Fardon, Remi
A1 Parsons, Loren H
K1 FAAH
K1 Microdialysis
K1 Nicotine
AB Nicotine exerts its rewarding effects by promoting an increase in dopamine (DA) release in the nucleus accumbens (NAc), and this process is influenced by the endocannabinoid system. Fatty acid amide hydrolase (FAAH) is the main enzyme responsible for the degradation of the endocannabinoid anandamide and other non-cannabinoid N-acylethanolamines. Previous research has reported that both genetic deletion and pharmacological inhibition of FAAH enhance nicotine-induced conditioned place preference at low doses. We conducted a microdialysis study to characterize nicotine-induced changes in DA and serotonin (5-HT) levels in the NAc of FAAH knockout (KO) mice using a conditioned place preference-like paradigm with three nicotine doses (0.1, 1 and 10 mg/kg, s.c.). Additionally, the effects of the selective FAAH inhibitor PF-3845 (10 mg/kg, i.p.) were also examined. Our data indicated that compared with wild-type mice, genetic deletion of FAAH selectively enhanced the effect of low-dose nicotine on DA release (p < 0.001), which resulted in a sustained increase in DA levels (p < 0.05).Similar to FAAH KO mice, PF-3845-pretreated mice displayed a moderate enhancement of the effect of low-dosenicotine on NAc 5-HT release (p < 0.01). These observations in mice suggest that enhanced nicotine-induced NAcDA release might contribute to increased sensitivity to the conditioned rewarding effects of low-dose nicotine followingFAAH inhibition, which has been previously reported. Future studies combining behavioral and neurochemicalapproaches are needed to elucidate the precise mechanism of these effects.
YR 2018
FD 2018-02-14
LK http://hdl.handle.net/10668/11358
UL http://hdl.handle.net/10668/11358
LA en
NO Pavon FJ, Serrano A, Sidhpura N, Polis I, Stouffer D, de Fonseca FR, et al. Fatty acid amide hydrolase (FAAH) inactivation confers enhanced sensitivity to nicotine-induced dopamine release in the mouse nucleus accumbens. Addict Biol. 2018 Mar;23(2):723-734
NO The present study has been supportedby the following grants: Instituto de Salud Carlos III (ISCIII) and European Regional Development Funds-European Union (ERDF-EU) (Subprograma RETICS Redde Trastornos Adictivos RD12/0028/0001); Junta deAndalucía, Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI CTS-433); and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) (grant no.AA020404 and AA022249). FJP and AS hold a ‘MiguelServet’ research contract funded by ISCIII and ERDF-EU(CP14/00212 and CP14/00173, respectively).
DS RISalud
RD Apr 13, 2025