Hamouda, Ayman K.Jackson, AstiDamaj, M. Imad2024-03-292024-03-292018-07Hamouda, A. K. vd. (2018). ''Reversal of nicotine withdrawal signs through positive allosteric modulation of α4β2 nicotinic acetylcholine receptors in male mice''. Nicotine and Tobacco Research, 20(7), 903-907.1462-22031469-994Xhttps://academic.oup.com/ntr/article/20/7/903/4084707https://hdl.handle.net/11452/40689Introduction: Nicotine withdrawal symptoms are important factors in determining the relapse rate to tobacco smoking and drugs that diminish these symptoms would potentially have a higher success rate as smoking cessation aids. Unlike US Food and Drug administration approved smoke cessation aids (nicotine and varenicline) which act as nicotinic acetylcholine receptors (nAChRs) agonists, desformylflustrabromine (dFBr) acts as a nAChR positive allosteric modulator with higher selectivity to the alpha 4 ss 2 nAChR. In animal studies, dFBr was well tolerated and reduced intravenous nicotine self-administration. In this study, we use behavioral test in mouse model of spontaneous nicotine withdrawal to assess the effect of dFBr on nicotine withdrawal symptoms. Methods: Spontaneous nicotine withdrawal in nicotine-dependent ICR male mice was established 18-24 h after termination (minipump removal) of 14 days infusion of nicotine. After that (day 15), spontaneous signs of nicotine withdrawal were examined in the following order: anxiety-like behaviors, somatic signs, and then hyperalgesia using previously published behavioral protocols. Fifteen minutes before withdrawal signs testing, mice received a subcutaneous acute injection of vehicle or dFBr at the doses of 0.02, 0.1, and 1 mg/kg to determine the effect of dFBr on nicotine withdrawal symptoms. Results: dFBr produced dose-dependent reversal of nicotine withdrawal signs in mouse model of spontaneous nicotine withdrawal. Implications: Positive allosteric modulators of nAChR such as dFBr reduce nicotine withdrawal symptoms supporting the potential clinical use of this novel class of nAChR-based therapeutics as smoking cessation aid.eninfo:eu-repo/semantics/closedAccessSubstance abusePublic, environmental & occupational healthSmoking-cessationBeta-2 subunitAlpha-4-beta-2AddictionDesformylflustrabromineNeurobiologyBrainAllosteric regulationAnimalsHydrocarbons, brominatedIndole alkaloidsInfusion pumps, implantableMaleMiceMice, inbred ICRNicotineNicotinic agonistsReceptors, nicotinicSmoking cessationSubstance withdrawal syndromeVareniclineArticle0004348574000162-s2.0-8504082785690390720729059422https://doi.org/10.1093/ntr/ntx183Substance abusePublic, environmental & occupational healthNicotinic Receptors; Animals; MethyllycaconitineDesformylflustrabromineNicotinic agentNicotinic receptor alpha4beta2Unclassified drugBrominated hydrocarbonDesformylflustrabromineIndole alkaloidNicotineNicotinic agentNicotinic receptorNicotinic receptor alpha4beta2VareniclineAllosterismAnimal experimentAnimal modelAnxietyArticleControlled studyDose responseDrug dose comparisonDrug mechanismExperimental behavioral testHyperalgesiaIn vivo studyMaleMouseMouse modelNeuromodulationNonhumanPriority journalPsychosomatic disorderSmoking cessationWithdrawal syndromeAllosterismAnimalDrug effectImplantable infusion pumpInstitute for Cancer Research mousePathophysiologyPhysiologyProceduresWithdrawal syndrome