Role of nicotine on cognitive and behavioral deficits in sepsis-surviving rats

Sepsisanditscomplicationsareimportantcausesofmortalityinintensivecareunitsand sepsis survivorsmaypresentlong-termcognitiveandemotionalimpairments,including memory deficitsandanxietysymptoms.Inthepresentstudy,weinvestigatedwhether repeatednicotineadministrationcanaffectthebehavioralchangesinsepsis-surviving rats. MaleWistarratsweredividedintwogroups:sham-operatedandexperimentalsepsis induced bycecalligationandpuncture(CLP).Theanimalswereinjectedsubcutaneously with nicotine(0.1mg/kg)orvehicleonceadayduring1weekbeforeand/or1weekafter sepsis induction.Thirtyminutesafterthelastadministration(i.e.,7daysaftersurgery),the animals weretestedintheopenfield,elevatedplus-mazeandstep-downinhibitory avoidancetasks.Therepeatednicotinetreatmentdidnotaffectthesurvivalrateinthe sepsis group(50%).Moreover,nosignificantchangesonlocomotoractivitywereobserved in thesepsisgroupwhilethetreatmentwithnicotineduring1weekaftersurgeryreduced the locomotionofsepsis-survivingratsintheopenfield.Itisimportanttonotethatboth schedules ofnicotinetreatment(priorand/orafterCLP)improvedthesepsis-induced anxiogenic-likeresponses.Interestingly,nicotinewasabletoimproveshort-andlong-term inhibitory avoidancememoryimpairments,observedinsepsissurvivors,onlywhen administered during2consecutiveweeks(i.e.,priorandafterCLP).Takentogether,these resultsindicatethatrepeatednicotineadministrationdoesnotalterthesurvivalratein rats submittedtoCLPandprovidenewevidencethatnicotinecanimprovelong-lasting memory impairmentsandanxiogenic-likeresponsesinsepsis-survivinganimals.