Effects of nicotine on the amplitude and gating of the auditory P50 and its influence by dopamine D2 receptor gene polymorphism.
Evidence of normalized auditory P50 suppression with acute nicotine in schizophrenia has supported the contention that elevated smoking rates in this disorder may be an attempt to correct a nicotinic receptor pathophysiology that may underly impaired sensory gating in these patients. There is very little information regarding the neurochemical or genetic pathways through which nicotine regulates P50 amplitude and its suppression in human studies. In a randomized, double-blind, placebo-controlled design with 24 non-smokers, this study examined the influence of TaqIA dopamine D2 receptor gene polymorphisms on P50 and its inhibition during nicotine gum (6 mg) administration. Within a paired click (S(1)-S(2)) paradigm, placebo treated A1(+) and A1(-) allele groups differed with respect to P50 amplitude and gating. While nicotine (relative to placebo) attenuated S(1) P50 amplitude in A1(+) allele carriers, in the A1(-) carriers it increased S(2) P50 amplitude and increased P50 gating as indexed by an augmented gating difference wave (GDW). These findings suggest that nicotine exerts mixed gating properties in healthy nicotine naive volunteers and that dopamine functions to alter both P50 and its gating as well as their response to acute nicotine agonist treatment.
Knott
V
V
University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada. vknott@rohcg.on.ca
Millar
A
A
Fisher
D
D
Albert
P
P
D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004298:Dopamine / Q000378:metabolism*; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D010919:Placebos; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000235:genetics; D055139:Sensory Gating / Q000187:drug effects* / Q000235:genetics; D014029:Tobacco Use Disorder / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
D018722:Nicotinic Agonists; D010919:Placebos; D017448:Receptors, Dopamine D2; D009538:Nicotine; D004298:Dopamine