Publication:
Fatty acid amide hydrolase (FAAH) inactivation confers enhanced sensitivity to nicotine-induced dopamine release in the mouse nucleus accumbens.

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2018-02-14

Authors

Pavon, Francisco J
Serrano, Antonia
Sidhpura, Nimish
Polis, Ilham
Stouffer, David
Rodriguez-de-Fonseca, Fernando
Cravatt, Benjamin F
Martin-Fardon, Remi
Parsons, Loren H

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Abstract

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.

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MeSH Terms

Amidohydrolases
Animals
Dopamine
Endocannabinoids
Mice
Mice, Knockout
Microdialysis
Nicotine
Nicotinic Agonists
Nucleus Accumbens
Piperidines
Pyridines

DeCS Terms

Nicotina
Serotonina
Ácidos Grasos
Microdiálisis
Predicción

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Keywords

FAAH, Microdialysis, Nicotine

Citation

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