Differential effects of nicotine on P50 amplitude, its gating, and their neural sources in low and high suppressors.
Sensory gating impairment in schizophrenia has been documented in the form of aberrant middle latency P50 event-related brain potential responses to S(1) and/or S(2) stimuli in a paired (S(1)-S(2)) auditory stimulus paradigm. Evidenced by a failure to suppress S(2) P50 or by attenuated S(1) P50s, these sensory deficits have been associated with increased smoking behaviour in this disorder, and may be related to the putative ameliorating effects of smoke-inhaled nicotine on neural mechanisms regulating gating. Comparison of healthy controls with low versus high gating efficiency has been forwarded as a model for investigating the actions of antipsychotic agents on aberrant gating functions. In the current study, the effect of a single dose (6 mg) of nicotine gum on P50, gating indices, and their cortical sources indexed with sLORETA (standardized low resolution electromagnetic tomography), was examined in healthy non-smokers (n=24) stratified for low and high gating levels. Scalp surface recordings revealed nicotine modulation of P50 and its gating to be differentially exhibited in high (decreasing gating) and low (increasing gating) suppressors while the underlying cortical sources influenced by nicotine (middle frontal gyrus, inferior/superior parietal lobules, pre- and post-central gyri) were seen only in low suppressors. These findings suggest that nicotine impacts sensory gating in healthy volunteers and as the gating enhancing effects were dependent on low baseline gating efficiency, nicotinic receptor agonists may be associated with unique P50 modulating actions in schizophrenia.
Knott
V J
VJ
University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada. vknott@rohcg.on.ca
Fisher
D J
DJ
Millar
A M
AM
D000161:Acoustic Stimulation / Q000379:methods; D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D055139:Sensory Gating / Q000187:drug effects*; D014054:Tomography / Q000379:methods
D018722:Nicotinic Agonists; D009538:Nicotine