Inhibition of fatty acid amide hydrolase reduces reinstatement of nicotine seeking but not break point for nicotine self-administration—comparison with CB1 receptor blockade

Forget, Benoît; Coen, Kathleen M.; Foll, Bernard Le

doi:10.1007/s00213-009-1569-5

Cited by 110 publications

(126 citation statements)

References 61 publications

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“…This is presumably the mechanism by which PPARa activation blocks the dopaminergic effects of nicotine in the VTA and nucleus accumbens shell, which are believed to provide the primary basis for nicotine reward (Gotti et al, 2010;Corrigall et al, 1994;Lecca et al, 2006). This nicotineinduced dopaminergic signaling, and indeed the rewarding effects of nicotine in behavioral procedures, have been shown to be blocked by experimental drugs that activate PPARa directly (ie, the synthetic agonist WY14643, the endogenous ligands oleoylethanolamine and palmitoylethanolamide, and the longer-acting oleoylethanolamine derivative methyl oleoylethanolamine; Melis et al, 2008Melis et al, , 2010Mascia et al, 2011) or indirectly (ie, the fatty-acid amide hydrolase inhibitor URB597; Melis et al, 2008;Scherma et al, 2008;Forget et al, 2009;Luchicchi et al, 2010). The electrophysiology, microdialysis, and behavioral experiments of this study extend these findings to the fibrate class of medications.…”

Section: Discussionmentioning

confidence: 99%

“…We have shown that experimental drugs that activate PPARa block nicotine-induced firing of dopamine neurons in the VTA and nicotine-induced elevations of extracellular dopamine levels in the nucleus accumbens shell of rats, and that they decrease nicotine-seeking behavior in rats and monkeys (Melis et al, 2008Scherma et al, 2008;Forget et al, 2009;Luchicchi et al, 2010;Mascia et al, 2011). These preclinical findings suggest that PPARa could be an effective target for anti-smoking medications.…”

Section: Introductionmentioning

confidence: 91%

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Novel Use of a Lipid-Lowering Fibrate Medication to Prevent Nicotine Reward and Relapse: Preclinical Findings

Panlilio

Justinová

Mascia

et al. 2012

Neuropsychopharmacol

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Experimental drugs that activate a-type peroxisome proliferator-activated receptors (PPARa) have recently been shown to reduce the rewarding effects of nicotine in animals, but these drugs have not been approved for human use. The fibrates are a class of PPARa-activating medications that are widely prescribed to improve lipid profiles and prevent cardiovascular disease, but these drugs have not been tested in animal models of nicotine reward. Here, we examine the effects of clofibrate, a representative of the fibrate class, on reward-related behavioral, electrophysiological, and neurochemical effects of nicotine in rats and squirrel monkeys. Clofibrate prevented the acquisition of nicotine-taking behavior in naive animals, substantially decreased nicotine taking in experienced animals, and counteracted the relapse-inducing effects of re-exposure to nicotine or nicotine-associated cues after a period of abstinence. In the central nervous system, clofibrate blocked nicotine's effects on neuronal firing in the ventral tegmental area and on dopamine release in the nucleus accumbens shell. All of these results suggest that fibrate medications might promote smoking cessation. The fact that fibrates are already approved for human use could expedite clinical trials and subsequent implementation of fibrates as a treatment for tobacco dependence, especially in smokers with abnormal lipid profiles.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Novel Use of a Lipid-Lowering Fibrate Medication to Prevent Nicotine Reward and Relapse: Preclinical Findings

Panlilio

Justinová

Mascia

et al. 2012

Neuropsychopharmacol

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“…Screening of two independent clinical populations revealed that CB 1 gene variants are associated with nicotine dependence (Chen et al, 2008) and the CB 1 receptor antagonist Rimonabant (SR141716A) prolonged abstinence rates in smokers expressing motivation to quit . SR141716A and the related CB 1 antagonist AM251 reduce nicotine selfadministration (SA) by rats (Cohen et al, 2002(Cohen et al, , 2005Forget et al, 2009;Shoaib, 2008), attenuate nicotine-induced increases in nucleus accumbens (NAc) dopamine (DA) (Cheer et al, 2007;Cohen et al, 2002;Grieder et al, 2012), and reduce reinstatement of nicotine-seeking behavior in animal models of relapse (Forget et al, 2009). Collectively, these findings provide strong evidence for a CB 1 receptor involvement in the motivational effects produced by nicotine, and imply a role for endocannabinoid (eCB) signaling in this process.…”

Section: Introductionmentioning

confidence: 93%

“…For example, although synthetic CB 1 agonists increase nicotine SA and enhance nicotine-seeking behavior (Gamaleddin et al, 2012), these nicotine-related behaviors are generally attenuated by enhancing endogenous eCB tone (eg, eCB clearance inhibition) (Forget et al, 2009;Gamaleddin et al, 2011;Scherma et al, 2008). The distinction between these influences may arise, in part, from differential regional patterns of CB1 activation.…”

Section: Endocannabinoid Levels Following Nicotine Exposure Mw Buczynmentioning

confidence: 99%

“…Moreover, in contrast to CB 1 -selective agonists, manipulations such as FAAH inhibition also enhance signaling through non-CB receptors (PPAR a , TRPV 1 , and so on) that may counter or modify the effects of concurrent CB 1 receptor signaling. Because the nature of nicotine-induced alterations in eCB signaling may differ at various stages of nicotine exposure (eg, acquisition vs maintenance of drug intake; dependence), and nicotineinduced eCB alterations may differ from eCB disruptions associated with nicotine-seeking behavior (induced by cues, drug priming, and/or stress), it is not surprising that the influence of eCB clearance inhibition on nicotine-related behaviors varies among these distinct phases of nicotine use (Forget et al, 2009;Scherma et al, 2008).…”

Section: Endocannabinoid Levels Following Nicotine Exposure Mw Buczynmentioning

confidence: 99%

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The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

Buczynski

Polis

Parsons

2012

Neuropsychopharmacol

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Cannabinoid-1 receptors (CB 1 ) have an important role in nicotine reward and their function is disrupted by chronic nicotine exposure, suggesting nicotine-induced alterations in endocannabinoid (eCB) signaling. However, the effects of nicotine on brain eCB levels have not been rigorously evaluated. Volitional intake of nicotine produces physiological and behavioral effects distinct from forced drug administration, although the mechanisms underlying these effects are not known. This study compared the effects of volitional nicotine self-administration (SA) and forced nicotine exposure (yoked administration (YA)) on levels of eCBs and related neuroactive lipids in the ventral tegmental area (VTA) and other brain regions. Brain lipid levels were indexed both by in vivo microdialysis in the VTA and lipid extractions from brain tissues. Nicotine SA, but not YA, reduced baseline VTA dialysate oleoylethanolamide (OEA) levels relative to nicotine-naïve controls, and increased anandamide (AEA) release during nicotine intake. In contrast, all nicotine exposure paradigms increased VTA dialysate 2-arachidonoyl glycerol (2-AG) levels. Thus, nicotine differentially modulates brain lipid (2-AG, AEA, and OEA) signaling, and these modulations are influenced by the volitional nature of the drug exposure. Corresponding bulk tissue analysis failed to identify these lipid changes. Nicotine exposure had no effect on fatty acid amide hydrolase activity in the VTA, suggesting that changes in AEA and OEA signaling result from alterations in their nicotine-induced biosynthesis. Both CB 1 (by AEA and 2-AG) and non-CB 1 (by OEA) targets can alter the excitability and activity of the dopaminergic neurons in the VTA. Collectively, these findings implicate disrupted lipid signaling in the motivational effects of nicotine.

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The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers

et al. 2020

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Introduction The cannabinoid CB1 receptor (CB1R) has been shown in preclinical studies to be involved in nicotine reinforcement and relapse‐like behavior. The common single nucleotide polymorphism (SNP) rs2023239 may code for an alternative CB1R protein, alter CB1R expression, and be involved in nicotine dependence. To date, no study has explored the relationship between this SNP in CB1R and specific phenotypes of nicotine dependence. Methods The current study investigated the influence of CB1R rs2023239 in nicotine reinforcement and craving in regular cigarette smokers. Current smokers (n = 104, cigarettes per day ≥ 10) were genetically grouped (C allele group vs. No C allele group) and underwent laboratory measures of nicotine reinforcement and smoking cue‐elicited craving. Nicotine reinforcement was assessed using a forced choice paradigm, while a cue‐reactivity procedure measured cue‐elicited craving. Results These results show that smokers with the C allele variant (CC + CT genotypes) experienced a lower nicotine reinforcement effect compared to those without the C allele (TT genotype). These results were similar in both our subjective and behavioral reinforcement measures, though the subjective effects did not withstand controlling for race. There was no difference between genotype groups with respect to cue‐elicited craving, suggesting a lack of influence in cue reactivity. Conclusion Taken together, these results suggest that the variation in the CB1R (i.e., rs2023239 SNP) may play a larger role in nicotine reinforcement compared to cue reactivity. This work provides impetus to further understand the physiological mechanisms that explain how CB1Rs influence nicotine dependence phenotypes.

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Inhibition of fatty acid amide hydrolase reduces reinstatement of nicotine seeking but not break point for nicotine self-administration—comparison with CB1 receptor blockade

Cited by 110 publications

References 61 publications

Novel Use of a Lipid-Lowering Fibrate Medication to Prevent Nicotine Reward and Relapse: Preclinical Findings

Novel Use of a Lipid-Lowering Fibrate Medication to Prevent Nicotine Reward and Relapse: Preclinical Findings

The Volitional Nature of Nicotine Exposure Alters Anandamide and Oleoylethanolamide Levels in the Ventral Tegmental Area

The CB1R rs2023239 receptor gene variant significantly affects the reinforcing effects of nicotine, but not cue reactivity, in human smokers

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