The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism
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ORIGINAL INVESTIGATION
The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism Nadine Petrovsky & Ulrich Ettinger & Henrik Kessler & Rainald Mössner & Steffen Wolfsgruber & Norbert Dahmen & Wolfgang Maier & Michael Wagner & Boris B. Quednow
Received: 2 November 2012 / Accepted: 20 March 2013 / Published online: 19 April 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Rationale Prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating, can be enhanced by nicotine. Moreover, the TT genotype of the nicotinic acetylcholine receptor (nAChR) α3-subunit (CHRNA3) rs1051730 polymorphism has previously been associated with diminished PPI and nicotine dependence. Objectives We tested whether this CHRNA3 polymorphism also modulates the nicotine-induced enhancement of PPI. Methods We assessed the effect of nicotine on PPI, startle reactivity, and habituation in 52 healthy nonsmoking volunteers genotyped for CHRNA3 rs1051730 in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Additionally, cotinine plasma levels were measured. Results Nicotine significantly enhanced PPI in TT homozygotes only and tended to worsen PPI in TC and CC carriers. Additionally, nicotine significantly reduced startle habituation. Conclusions The present findings imply that the effect of nicotine on sensorimotor gating is modulated by nAChR N. Petrovsky : H. Kessler : R. Mössner : S. Wolfsgruber : W. Maier : M. Wagner Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany N. Petrovsky (*) : U. Ettinger Department of Psychology, University of Bonn, Kaiser-Karl-Ring 9, 53111 Bonn, Germany e-mail: [email protected] N. Dahmen Department of Psychiatry, Johannes Gutenberg-University of Mainz, Mainz, Germany B. B. Quednow Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy, and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich, Switzerland
α3-subunits. Thus, genetic variation in nicotinic receptor genes might be an important connecting link between early attentional processes and smoking behavior. Keywords Prepulse inhibition . Sensorimotor gating . CHRNA3 . Nicotine . Nicotinic acetylcholine receptor . rs1051730
Introduction In humans, prepulse inhibition (PPI) is commonly measured as PPI of the acoustic startle reflex: a relatively weak and nonstartling noise (the prepulse) is presented 30–500 ms before a strong startle–eliciting sound (the pulse) resulting in a reduction of the eye-blink startle reflex (Graham 1975). More specifically, PPI is thought to reflect an automatic filtering process in which the processing of the prepulse is protected from disruption which leads to attenuated processing of the pulse (Baschnagel and Hawk 2008; Graham 1975). PPI is commonly viewed as an operational measure of a process called “sensorimotor gating,” by which excess or trivial stimuli are screened or “gated out” of awareness so that an individual can focus attention on the most salient aspe
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