Jackson, AstiMuldoon, Pretal P.Lichtman, Aron H.Carroll, F. IvyGreenwald, MarkMiles, Michael F.Damaj, M. Imad2022-12-232022-12-232017-03-04Jackson, A. vd. (2017). ''In vivo interactions between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-alpha: Implication for nicotine dependence''. Neuropharmacology, 118, 38-45.0028-3908https://doi.org/10.1016/j.neuropharm.2017.03.005https://www.sciencedirect.com/science/article/pii/S00283908173008861873-7064http://hdl.handle.net/11452/30059United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Drug Abuse (NIDA) - R01 DA12610 - R01 DA032246 - T32 DA007027-41United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) - P50AA022537United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Drug Abuse (NIDA) European Commission - T32DA007027 - R01DA032246 - R01DA012610Chronic tobacco use dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. The main addictive component of tobacco, nicotine, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). Activation of the homomeric alpha 7 nAChR reduces nicotine's rewarding properties in conditioned place preference (CPP) test and i.v. self-administration models, but the mechanism underlying these effects is unknown. Recently, the nuclear receptor peroxisome proliferator-activated receptor type-alpha (PPAR alpha) has been implicated as a downstream signaling target of the alpha 7 nAChR in ventral tegmental area dopamine cells. The present study investigated PPAR alpha as a possible mediator of the effect of alpha 7 nAChR activation in nicotine dependence. Our results demonstrate the PPAR alpha antagonist GW6471 blocks actions of the alpha 7 nAChR agonist PNU282987 on nicotine reward in an unbiased CPP test in male ICR adult mice. These findings suggests that alpha 7 nAChR activation attenuates nicotine CPP in a PPAR alpha-dependent manner. To evaluate PPAR alpha activation in nicotine dependence we used the selective and potent PPAR alpha agonist, WY-14643 and the clinically used PPAR alpha activator, fenofibrate, in nicotine CPP and we observed attenuation of nicotine preference, but fenofibrate was less potent. We also studied PPAR alpha in nicotine dependence by evaluating its activation in nicotine withdrawal. WY-14643 reversed nicotine withdrawal signs whereas fenofibrate had modest efficacy. This suggests that PPAR alpha plays a role in nicotine reward and withdrawal and that further studies are warranted to elucidate its function in mediating the effects of alpha 7 nAChRs in nicotine dependence.eninfo:eu-repo/semantics/openAccessNeurosciences & neurologyPharmacology & pharmacyNicotine dependenceBehavioral pharmacologyMiceConditioned place preferencePpar-alphaDopamine neuronsMiceRewardWithdrawalMouseDeficitsSubunitCocaineAlpha7 nicotinic acetylcholine receptorAnesthetics, localAnimalsBenzamidesBridged bicyclo compoundsCocaineConditioning, operantDisease models, animalFenofibrateHypolipidemic agentsMaleMiceMice, inbred ICRNicotineNicotinic agonistsOxazolesPPAR alphaPyrimidinesSelf administrationSubstance withdrawal syndromeTobacco use disorderTyrosineArticle0004016786000042-s2.0-85014872073384511828279662NeurosciencesPharmacology & pharmacyNicotinic Receptors; Animals; Methyllycaconitine4 chloro n (3 quinuclidinyl)benzamideBungarotoxin receptorFenofibrateNicotinePeroxisome proliferator activated receptor alphaPirinixic acidAntilipemic agentBenzamide derivativeBridged bicyclo compoundsBungarotoxin receptorCocaineFenofibrateGW 6471Local anesthetic agentNicotineNicotinic agentOxazole derivativePeroxisome proliferator activated receptor alphaPirinixic acidPNU-282987Pyrimidine derivativeYyrosineAdultAnimal experimentAnimal modelArticleConditioned place preference testControlled studyDrug effectDrug efficacyDrug potencyIn vivo studyMaleMouseNonhumanProtein protein interactionRewardSmoking cessationTobacco dependenceAgonistsAnalogs and derivativesAnimalAntagonists and inhibitorsDisease modelDrug effectsDrug self administrationInstitute for Cancer Research mouseInstrumental conditioningMetabolismTobacco dependenceWithdrawal syndrome