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The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism


Petrovsky, N; Ettinger, U; Kessler, H; Mössner, R; Wolfsgruber, S; Dahmen, N; Maier, W; Wagner, M; Quednow, Boris B (2013). The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism. Psychopharmacology, 229(1):31-40.

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 α3-subunits. Thus, genetic variation in nicotinic receptor genes might be an important connecting link between early attentional processes and smoking behavior.

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 α3-subunits. Thus, genetic variation in nicotinic receptor genes might be an important connecting link between early attentional processes and smoking behavior.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:19 April 2013
Deposited On:03 Jul 2013 13:33
Last Modified:22 Sep 2017 13:28
Publisher:Springer
ISSN:0033-3158
Publisher DOI:https://doi.org/10.1007/s00213-013-3081-1
PubMed ID:23604333

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