1. In vivo interactions between α7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-α: Implication for nicotine dependence
- Author
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Aron H. Lichtman, Mark K. Greenwald, Pretal P. Muldoon, Asti Jackson, Deniz Bagdas, Michael F. Miles, F. Ivy Carroll, M. Imad Damaj, Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Merkezi., and Bağdaş, Deniz
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Nicotine dependence ,Male ,0301 basic medicine ,Conditioning, operant ,Mouse ,Pyrimidine derivative ,Deficits ,Peroxisome proliferator-activated receptor ,Smoking cessation ,Antagonists and inhibitors ,Pharmacology ,Disease models, animal ,Tobacco use disorder ,Dopamine neurons ,Nicotine ,Mice ,In vivo study ,0302 clinical medicine ,Cocaine ,Fenofibrate ,Nicotinic Receptors ,Animals ,Methyllycaconitine ,Bungarotoxin receptor ,Drug self administration ,Behavioral pharmacology ,Pirinixic acid ,Oxazoles ,Ppar-alpha ,chemistry.chemical_classification ,GW 6471 ,Analogs and derivatives ,Benzamide derivative ,Nicotinic agent ,Conditioned place preference ,Ventral tegmental area ,Nicotinic agonist ,Nicotine withdrawal ,medicine.anatomical_structure ,Mice, inbred ICR ,Withdrawal ,Yyrosine ,Benzamides ,Institute for Cancer Research mouse ,medicine.drug ,Adult ,Agonist ,Subunit ,Anesthetics, local ,medicine.drug_class ,Alpha7 nicotinic acetylcholine receptor ,Conditioned place preference test ,Neurosciences & neurology ,Article ,PNU-282987 ,Self administration ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Drug potency ,Instrumental conditioning ,Reward ,Withdrawal syndrome ,Hypolipidemic agents ,medicine ,Bridged bicyclo compounds ,PPAR alpha ,Animal model ,Animal experiment ,Nicotinic agonists ,Substance withdrawal syndrome ,Acetylcholine receptor ,Local anesthetic agent ,Drug effects ,Pharmacology & pharmacy ,Animal ,Disease model ,Neurosciences ,Oxazole derivative ,Nonhuman ,medicine.disease ,Drug effect ,Drug efficacy ,Pyrimidines ,Metabolism ,030104 developmental biology ,chemistry ,Protein protein interaction ,Tyrosine ,Antilipemic agent ,Peroxisome proliferator activated receptor alpha ,Controlled study ,Tobacco dependence ,030217 neurology & neurosurgery ,4 chloro n (3 quinuclidinyl)benzamide ,Agonists - Abstract
United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Drug Abuse (NIDA) - R01 DA12610 - R01 DA032246 - T32 DA007027-41 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) - P50AA022537 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Drug Abuse (NIDA) European Commission - T32DA007027 - R01DA032246 - R01DA012610 Chronic 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.
- Published
- 2017
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