BACKGROUND: The uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, ketamine, induces a range of symptoms resembling those seen in schizophrenia. Enhancement of nicotinic acetylcholine receptor (nAChR) function may have potential as a treatment for the cognitive deficits and negative symptoms of schizophrenia. Accordingly, we examined the modulatory effects of brain nAChR systems on NMDAR antagonist-induced effects. METHODS: The interactive effects of ketamine and nicotine were evaluated in 37 healthy subjects in a randomized, placebo-controlled, double-blind, crossover counterbalanced, 2 (intravenous ketamine or placebo) × 2 (intravenous nicotine or placebo) design. Verbal and visual memory, sustained attention, working memory, response inhibition, emotion recognition, executive function, reaction time, motor function, and speed of processing were assessed once per test day, while negative and positive symptoms, perceptual alterations, and a number of feeling states were measured several times before and after administration of drugs. RESULTS:Ketamine induced cognitive deficits and negative and positive symptoms. Nicotine worsened immediate recall, auditory working memory, response inhibition, and executive function and serial processing. Nicotine decreased (improved) reaction time on the sustained attention and choice reaction time tasks. Nicotine did not reduce ketamine-induced cognitive deficits or negative and positive symptoms. CONCLUSIONS: At blood levels comparable with tobacco smoking, nicotine infusion does not appear to alleviate the ketamine-induced transient cognitive and behavioral effects in healthy subjects that resemble those seen in schizophrenia. The lack of an effect of nicotine on a spectrum of ketamine effects suggests that the consequences of NMDAR antagonism are not likely under the direct influence of nAChR.
RCT Entities:
BACKGROUND: The uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, ketamine, induces a range of symptoms resembling those seen in schizophrenia. Enhancement of nicotinic acetylcholine receptor (nAChR) function may have potential as a treatment for the cognitive deficits and negative symptoms of schizophrenia. Accordingly, we examined the modulatory effects of brain nAChR systems on NMDAR antagonist-induced effects. METHODS: The interactive effects of ketamine and nicotine were evaluated in 37 healthy subjects in a randomized, placebo-controlled, double-blind, crossover counterbalanced, 2 (intravenous ketamine or placebo) × 2 (intravenous nicotine or placebo) design. Verbal and visual memory, sustained attention, working memory, response inhibition, emotion recognition, executive function, reaction time, motor function, and speed of processing were assessed once per test day, while negative and positive symptoms, perceptual alterations, and a number of feeling states were measured several times before and after administration of drugs. RESULTS:Ketamine induced cognitive deficits and negative and positive symptoms. Nicotine worsened immediate recall, auditory working memory, response inhibition, and executive function and serial processing. Nicotine decreased (improved) reaction time on the sustained attention and choice reaction time tasks. Nicotine did not reduce ketamine-induced cognitive deficits or negative and positive symptoms. CONCLUSIONS: At blood levels comparable with tobacco smoking, nicotine infusion does not appear to alleviate the ketamine-induced transient cognitive and behavioral effects in healthy subjects that resemble those seen in schizophrenia. The lack of an effect of nicotine on a spectrum of ketamine effects suggests that the consequences of NMDAR antagonism are not likely under the direct influence of nAChR.
Authors: Holly K Hamilton; Deepak C D'Souza; Judith M Ford; Brian J Roach; Naomi S Kort; Kyung-Heup Ahn; Savita Bhakta; Mohini Ranganathan; Daniel H Mathalon Journal: Schizophr Res Date: 2017-07-12 Impact factor: 4.939
Authors: Naomi S Kort; Judith M Ford; Brian J Roach; Handan Gunduz-Bruce; John H Krystal; Judith Jaeger; Robert M G Reinhart; Daniel H Mathalon Journal: Biol Psychiatry Date: 2016-07-01 Impact factor: 13.382
Authors: Daniel C Javitt; Cameron S Carter; John H Krystal; Joshua T Kantrowitz; Ragy R Girgis; Lawrence S Kegeles; John D Ragland; Richard J Maddock; Tyler A Lesh; Costin Tanase; Philip R Corlett; Douglas L Rothman; Graeme Mason; Maolin Qiu; James Robinson; William Z Potter; Marlene Carlson; Melanie M Wall; Tse-Hwei Choo; Jack Grinband; Jeffrey A Lieberman Journal: JAMA Psychiatry Date: 2018-01-01 Impact factor: 21.596
Authors: Mei Huang; Anna R Felix; Sunoh Kwon; David Lowe; Tanya Wallace; Luca Santarelli; Herbert Y Meltzer Journal: Psychopharmacology (Berl) Date: 2013-12-07 Impact factor: 4.530