Nicotine effects in adolescence and adulthood on cognition and α₄β₂-nicotinic receptors in the neonatal ventral hippocampal lesion rat model of schizophrenia

dc.contributor.authorBerg, Sarah A.
dc.contributor.authorSentir, Alena M.
dc.contributor.authorBell, Richard L.
dc.contributor.authorEngleman, Eric A.
dc.contributor.authorChambers, R. Andrew
dc.contributor.departmentDepartment of Psychiatry, IU School of Medicineen_US
dc.date.accessioned2016-10-17T13:38:10Z
dc.date.available2016-10-17T13:38:10Z
dc.date.issued2015-05
dc.description.abstractRational Nicotine use in schizophrenia has traditionally been explained as ‘self-medication’ of cognitive and/or nicotinic acetylcholinergic receptor (nAChR) abnormalities. Objectives We test this hypothesis in a neurodevelopmental rat model of schizophrenia that shows increased addiction behaviors including enhanced nicotine reinforcement and drug-seeking. Methods Nicotine transdermal patch (5 mg/kg/day vs. placebo × 10 days in adolescence or adulthood) effects on subsequent radial-arm maze learning (15 sessions) and frontal-cortical-striatal nAChR densities (α4β2; [3H]-epibatidine binding) were examined in neonatal ventral hippocampal lesion (NVHL) and SHAM-operated rats. Results NVHL cognitive deficits were not differentially affected by nicotine history compared to SHAMs. Nicotine history produced minimal cognitive effects while increasing food–reward consumption on the maze, compounding with NVHL-induced overconsumption. Acute nicotine (0.5 mg/kg) delivered before the final maze sessions produced modest improvements in maze performance in rats with nicotine patch histories only, but not differentially so in NVHLs. Consistent with in vivo neuroimaging of β2 nAChR binding in schizophrenia smokers vs. non-smokers and healthy controls, adult NVHLs showed 12% reductions in nAChR binding in MPFC (p<0.05) but not ventral striatum (<5% changes, p>.40), whereas nicotine history elevated nAChRs across both regions (>30%, p<0.001) without interacting with NVHLs. Adolescent vs. adult nicotine exposure did not alter nAChRs differentially. Conclusions Although replicating nicotine-induced up-regulation of nAChRs in human smokers and demonstrating NVHL validity in terms of schizophrenia-associated nAChR density patterns, these findings do not support hypotheses explaining increased nicotine use in schizophrenia as reflecting illness-specific effects of nicotine to therapeutically alter cognition or nAChR densities.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationBerg SA, Sentir AM, Bell RL, Engleman EA, Chambers RA. Nicotine Effects in Adolescence and Adulthood on Cognition and α4β2-Nicotinic Receptors in the Neonatal Ventral Hippocampal Lesion Rat Model of Schizophrenia. Psychopharmacology. 2015;232(10):1681-1692. doi:10.1007/s00213-014-3800-2en_US
dc.identifier.urihttps://hdl.handle.net/1805/11173
dc.language.isoen_USen_US
dc.publisherSpringeren_US
dc.relation.isversionof10.1007/s00213-014-3800-2en_US
dc.relation.journalPsychopharmacologyen_US
dc.sourcePMCen_US
dc.subjectAdministration, Cutaneousen_US
dc.subjectAge Factorsen_US
dc.subjectAnimalsen_US
dc.subjectCognition/drug effectsen_US
dc.subjectDisease Models, Animalen_US
dc.titleNicotine effects in adolescence and adulthood on cognition and α₄β₂-nicotinic receptors in the neonatal ventral hippocampal lesion rat model of schizophreniaen_US
dc.typeArticleen_US
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