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dc.contributor.authorHahn, B.
dc.contributor.authorShrieves, M.E.
dc.contributor.authorOlmstead, C.K.
dc.contributor.authorYuille, M.B.
dc.contributor.authorChiappelli, J.J.
dc.contributor.authorPereira, E.F.R.
dc.contributor.authorAlbuquerque, E.X.
dc.contributor.authorFawcett, W.P.
dc.date.accessioned2019-11-20T15:51:41Z
dc.date.available2019-11-20T15:51:41Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85074785724&doi=10.1007%2fs00213-019-05363-4&partnerID=40&md5=818561834b93dd8d5a19260383005dbb
dc.identifier.urihttp://hdl.handle.net/10713/11425
dc.description.abstractRationale: Cognitive benefits of nicotinic acetylcholine receptor (nAChR) agonists are well established but have generally been of small magnitude and uncertain clinical significance. A way of raising the effect size may be to facilitate agonist-induced responses by co-administering a nAChR positive allosteric modulator (PAM). Objective: The aim was to test whether galantamine, a PAM at several nAChR subtypes, can potentiate the cognitive-enhancing effects of nicotine. Methods: Twenty-six adult never-smokers were treated, in a double-blind counterbalanced sequence, with nicotine (7 mg/24 h, transdermally) and galantamine (4 mg, p.o.) combined, nicotine alone, galantamine alone, and double placebo. A low dose of galantamine was chosen to minimize acetylcholinesterase inhibition, which was verified in blood assays. In each condition, participants were tested with three cognitive tasks. Results: Nicotine significantly improved reaction time (RT) and signal detection in a visuospatial attention task and the Rapid Visual Information Processing Task. Galantamine did not modulate these effects. A trend toward RT reduction by galantamine correlated with acetylcholinesterase inhibition. In a change detection task, there were no effects of nicotine or galantamine alone on accuracy or RT. However, both drugs combined acted synergistically to reduce RT. This effect was not associated with acetylcholinesterase inhibition. Conclusions: A pattern consistent with allosteric potentiation of nicotine effects by galantamine was observed on one of six performance measures. This may reflect specific nAChR subtype involvement, or additional pharmacological actions of galantamine may have overshadowed similar interactions on other measures. The finding suggests that allosteric potentiation of nAChR agonist-induced cognitive benefits is possible in principle. Copyright 2019, The Author(s).en_US
dc.description.sponsorshipThis work was funded by NIH grant R01DA035813 to B. Hahn.en_US
dc.description.urihttps://doi.org/10.1007/s00213-019-05363-4en_US
dc.language.isoen_USen_US
dc.publisherSpringer Verlagen_US
dc.relation.ispartofPsychopharmacology
dc.subjectAttentionen_US
dc.subjectCDTen_US
dc.subjectCognitionen_US
dc.subjectGalantamineen_US
dc.subjectNicotineen_US
dc.subjectNon-smokersen_US
dc.subjectPositive allosteric modulatoren_US
dc.subjectRVIPen_US
dc.subjectSARATen_US
dc.titleEvidence for positive allosteric modulation of cognitive-enhancing effects of nicotine in healthy human subjectsen_US
dc.typeArticleen_US
dc.identifier.doi10.1007/s00213-019-05363-4
dc.identifier.pmid31686175


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