AUTHOR=Knott Verner , Shah Dhrasti , Millar Anne , McIntosh Judy , Fisher Derek , Villeneuve Crystal , Ilivitsky Vadim 

TITLE=Nicotine, Auditory Sensory Memory, and sustained Attention in a Human Ketamine Model of Schizophrenia: Moderating Influence of a Hallucinatory Trait

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 3 - 2012

YEAR=2012

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2012.00172

DOI=10.3389/fphar.2012.00172

ISSN=1663-9812

ABSTRACT=Background: The procognitive actions of the nicotinic acetylcholine receptor (nAChR) agonist nicotine are believed, in part, to motivate the excessive cigarette smoking in schizophrenia, a disorder associated with deficits in multiple cognitive domains, including low level auditory sensory processes and higher order attention-dependent operations.  Objectives:  As N-methyl-D-aspartate receptor (NMDAR) hypofunction has been shown to contribute to these cognitive impairments, the primary aims of this healthy volunteer study were to:  a) to shed light on the separate and interactive roles of nAChR and NMDAR systems in the modulation of auditory sensory memory (and sustained attention), as indexed by the auditory event-related brain potential (ERP) – mismatch negativity (MMN), and b) to examine how these effects are moderated by a predisposition to auditory hallucinations/delusions (HD).  Methods:  In a randomized, double-blind, placebo controlled design involving a low intravenous dose of ketamine (.04 mg/kg) and a 4 mg dose of nicotine gum, MMN and performance on a rapid visual information processing (RVIP) task of sustained attention were examined in 24 healthy controls psychometrically stratified as being lower (L-HD, n = 12) or higher (H-HD) for HD propensity.  Results:    Ketamine significantly slowed MMN, and reduced MMN in H-HD, with amplitude attenuation being blocked by the co-administration of nicotine.  Nicotine significantly enhanced response speed (reaction time) and accuracy (increased % hits and d΄ and reduced false alarms) on the RIVIP, with improved performance accuracy being prevented when nicotine was administered with ketamine.  Both % hits and d΄, as well as reaction time were poorer in H-HD (vs. L-HD) and while hit rate and d΄ was increased by nicotine in H-HD, reaction time was slowed by ketamine in L-HD.  Conclusions:  Nicotine alleviated ketamine-induced sensory memory impairments and improved attention, particularly in individuals prone to HD.