Behavioral and Molecular Analysis of Nicotine-Conditioned Place Preference in Zebrafish.docVIP

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Behavioral and Molecular Analysis of Nicotine-Conditioned Place Preference in Zebrafish.doc

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Behavioral and Molecular Analysis of Nicotine-Conditioned Place Preference in Zebrafish

BehavioralandMolecularAnalysisofNicotine- ConditionedPlacePreferenceinZebrafish XimenaKedikian1,MariaPaulaFaillace1,3,Ramo′nBernabeu1,2 * 1Departamento de Fisiolog?′a, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina, 2Instituto de Biolog?′a Celular y Neurociencias (IBCN- CONICET),Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina, 3Instituto deQu?′mica y Fisicoqu?′mica Biolo′gicas (IQUIFIB)-CONICET,Buenos Aires,Argentina Abstract Studies using mice and rats have demonstrated that nicotine induces a conditioned place preference (CPP), with more effectiveresultsobtainedbyusingbiasedprocedures.Zebrafishhavealsobeenusedasamodelsystemtoidentifyfactors influencing nicotine-associated reward by using an unbiased design. Here, we report that zebrafish exhibited putative nicotine biased CPP to an initially aversive compartment (nicotine-paired group). A counterbalanced nicotine-exposed controlgroupdidnotshowasignificantpreferenceshift,providingevidencethatthepreferenceshiftinthenicotine-paired groupwasnotduetoareductionofaversionforthiscompartment.Zebrafishpreferencewascorroboratedbybehavioral analysisofseveralindicatorsofdrugpreference,suchastimespentinthedrug-pairedside,numberofentriestothedrug- pairedside,anddistancetraveled.Theseresultsprovidedstrongevidencethatzebrafishmayactuallydevelopapreference for nicotine, although the drug was administrated in an aversive place for the fish, which was further supported by molecularstudies.Reversetranscription-quantitativereal-timePCRanalysisdepictedasignificantincreaseintheexpression ofa7anda6butnota4andb2subunitsofthenicotinicreceptorinnicotine-pairedzebrafishbrains.Incontrast,zebrafish brains from the counterbalanced nicotine group showed no significant changes. Moreover, CREB phosphorylation, an indicatorofneuralactivity,accompaniedtheacquisitionofnicotine-CPP.Ourstudiesofferedanincrementalvaluetothe drugaddictionfield,becausetheyfurtherdescribebehavioralfeaturesofCPPtonicot