title: Baseline dependency of nicotine's sensory gating actions: similarities and differences in low, medium and high P50 suppressors.
abstract: Reduced suppression of the P50 auditory event-related potential in schizophrenia patients relative to normal controls is indicative of a sensory gating deficit and is one of the most robust findings reported for functional brain abnormalities in this disorder. However, there is considerable gating variability in patients and controls and there is little understanding as to how inter-individual differences moderate gating responses to drugs and nicotinic agonists in particular, which have shown potential to reverse gating deficits. In this study the effects of acutely administered nicotine (gum, 6 mg) on sensory gating in a paired (S₁-S₂) auditory stimulus paradigm were investigated in 57 healthy, non-smoking volunteers stratified as low (n = 19), medium (n = 19) and high (n = 19) P50 suppressors on the basis of three separate baseline derived gating indices, P50 ratios, P50 difference scores, and gating difference waveforms. Relative to placebo, nicotine consistently improved gating in low suppressors as stratified with all three gating indices, exerted no effects in medium suppressors and reduced gating in high suppressors. Analysis of individual stimulus (S₂, S₂) amplitudes showed distinctly different mechanisms of action underlying nicotine effects in individuals with low and high baseline suppression. The results parallel similar findings of baseline-dependency in the gating effects of several antipsychotic drugs in healthy volunteers and support the use of group segmentation as a translational model in novel cognitive drug development for schizophrenia.
authors.affiliation: University of Ottawa Institute of Mental Health Research, Ottawa, Canada. verner.knott@theroyal.ca
authors.forename: Verner
authors.initials: V
authors.lastname: Knott
authors.forename: Sara
authors.initials: S
authors.lastname: de la Salle
authors.forename: Dylan
authors.initials: D
authors.lastname: Smith
authors.forename: Tristan
authors.initials: T
authors.lastname: Phillipe
authors.forename: Heather
authors.initials: H
authors.lastname: Dort
authors.forename: Joelle
authors.initials: J
authors.lastname: Choueiry
authors.forename: Danielle
authors.initials: D
authors.lastname: Impey
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000328:Adult; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004311:Double-Blind Method; D005071:Evoked Potentials / Q000187:drug effects; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D064368:Healthy Volunteers; D006801:Humans; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000494:pharmacology; D012559:Schizophrenia / Q000503:physiopathology; D055139:Sensory Gating / Q000187:drug effects*; D055815:Young Adult
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine
keywords: Nicotine; P50 suppression; nicotinic receptors; schizophrenia; sensory gating