Inhibition of FAAH and activation of PPAR: New approaches to the treatment of cognitive dysfunction and drug addiction

Panlilio, Leigh V.; Justinová, Zuzana; Goldberg, Steven R.

doi:10.1016/j.pharmthera.2013.01.003

Cited by 95 publications

(84 citation statements)

References 316 publications

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“…In previous work, URB597 is found to increase sucrose preference in stress-exposed animals, probably due to its "antidepression" properties [Rademacher and Hillard, 2007;Bortolato et al, 2007]. Consistent with studies on cocaine, nicotine and opioid seeking behaviour [Panlilio et al, 2013;Sloan et al, 2017], our findings show initial, promising data that FAAH inhibitors decrease alcohol excessive drinking, and "relapse" drinking in both male and female mice. Consistently, a new report demonstrates that the CeA of alcohol-preferring rats is involved in the URB597 effect on [Gobbi et al, 2005], have the potential to become useful compounds for treating alcoholism [Zhou et al, 2017c;Stopponi et al, 2018].…”

Section: Endocannabinoid Systemsupporting

confidence: 90%

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

Zhou

Kreek

2018

J Pharmacol Exp Ther

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Addiction to specific drugs (such as alcohol, psychostimulants and opioids) shares some common direct or downstream effects on the brain stress-responsive systems, including arginine vasopressin and its V1b receptors, dynorphin and the kappa opioid receptors, proopiomelanocortin/β-endorphin and the mu opioid receptors, and the endocannabinoids. Further study of these systems, through laboratory-based and translational research, could lead to the discovery of novel treatment targets and the early optimization of interventions (for example, combination) for the pharmacological therapy of alcoholism.

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Section: Endocannabinoid Systemsupporting

confidence: 90%

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

Zhou

Kreek

2018

J Pharmacol Exp Ther

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“…Modulating the activity of the endogenous cannabinoid system has the potential to produce therapeutic effects for a wide range of medical and psychiatric disorders (Moreira and Lutz, 2008;Panlilio et al, 2013;Zanettini et al, 2011). One strategy for achieving such effects is to administer drugs that bind to cannabinoid CB 1 receptors.…”

Section: Introductionmentioning

confidence: 99%

Effects of Fatty Acid Amide Hydrolase (FAAH) Inhibitors in Non-Human Primate Models of Nicotine Reward and Relapse

Justinová

Panlilio

Moreno-Sanz

et al. 2015

Neuropsychopharmacol

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Inhibition of the enzyme fatty acid amide hydrolase (FAAH) counteracts reward-related effects of nicotine in rats, but it has not been tested for this purpose in non-human primates. Therefore, we studied the effects of the first-and second-generation O-arylcarbamatebased FAAH inhibitors, URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester) and URB694 (6-hydroxy-[1,1'-biphenyl]-3-ylcyclohexylcarbamate), in squirrel monkeys. Both FAAH inhibitors: (1) blocked FAAH activity in brain and liver, increasing levels of endogenous ligands for cannabinoid and α-type peroxisome proliferator-activated (PPAR-α) receptors; (2) shifted nicotine self-administration dose-response functions in a manner consistent with reduced nicotine reward; (3) blocked reinstatement of nicotine seeking induced by reexposure to either nicotine priming or nicotine-associated cues; and (4) had no effect on cocaine or food self-administration. The effects of FAAH inhibition on nicotine self-administration and nicotine priming-induced reinstatement were reversed by the PPAR-α antagonist, MK886. Unlike URB597, which was not self-administered by monkeys in an earlier study, URB694 was self-administered at a moderate rate. URB694 self-administration was blocked by pretreatment with an antagonist for either PPAR-α (MK886) or cannabinoid CB 1 receptors (rimonabant). In additional experiments in rats, URB694 was devoid of THC-like or nicotine-like interoceptive effects under drug-discrimination procedures, and neither of the FAAH inhibitors induced dopamine release in the nucleus accumbens shell-consistent with their lack of robust reinforcing effects in monkeys. Overall, both URB597 and URB694 show promise for the initialization and maintenance of smoking cessation because of their ability to block the rewarding effects of nicotine and prevent nicotine priming-induced and cue-induced reinstatement.

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“…The FAAH inhibitors can produce their effects through PPARα and through cannabinoid CB1-receptors [26].…”

Section: Plasma Level Of Corticosterone (а) Testosterone (в) Epinepmentioning

confidence: 99%

Antistress effects of N-stearoylethanolamine in rats with chronic social stress

Horid’ko¹,

Kosiakova²,

Berdyshev³

2017

Ukr.Biochem.J.

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Inhibition of FAAH and activation of PPAR: New approaches to the treatment of cognitive dysfunction and drug addiction

Cited by 95 publications

References 316 publications

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

Effects of Fatty Acid Amide Hydrolase (FAAH) Inhibitors in Non-Human Primate Models of Nicotine Reward and Relapse

Antistress effects of N-stearoylethanolamine in rats with chronic social stress

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