Attenuation of the prepulse inhibition of the acoustic startle response within and between sessions

Quednow, Boris B.; Kühn, Kai‐Uwe; Beckmann, Katrin; Westheide, Jens; Maier, Wolfgang; Wagner, Michael

doi:10.1016/j.biopsycho.2005.05.001

Cited by 34 publications

(23 citation statements)

References 42 publications

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“…A second limitation is that we did not assess severity of smoking behavior in the schizophrenia sample assessed in Bonn. However, in contrast to some previous studies (Duncan et al, 2001;Swerdlow et al, 2006), the method that we used in Bonn was less susceptible to the effects of smoking status on PPI, whereas it was proven sensitive to psychopathological modulations of PPI (Quednow et al, 2006a(Quednow et al, , b, c, 2008a. This might have two reasons: (1) smoking withdrawal can decrease PPI (George et al, 2006;Kumari and Gray, 1999), but our subjects were allowed to smoke ad libitum before testing; (2) heavy smokers with schizophrenia display higher PPI levels than light-or non-smoking patients (Swerdlow et al, 2006), which is in line with the finding that nicotine itself could enhance PPI (Kumari et al, 1997;Postma et al, 2006).…”

Section: Discussionmentioning

confidence: 76%

Sensorimotor Gating is Associated with CHRNA3 Polymorphisms in Schizophrenia and Healthy Volunteers

Petrovsky

Quednow

Ettinger

et al. 2010

Neuropsychopharmacol

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Attentional gating deficits, commonly measured by prepulse inhibition (PPI) of the acoustic startle response (ASR), have been established as an endophenotype of schizophrenia. Prepulse inhibition is heritable and has been associated with polymorphisms in serotonin and dopamine system genes. Prepulse inhibition can be enhanced by nicotine, and therefore it has been proposed that schizophrenia patients smoke to ameliorate their early attentional deficits. The PPI-enhancing effects of nicotine in rodents are strain dependent, suggesting a genetic contribution to PPI within the nicotinic acetylcholine receptor (nAChR) system. Recent human genetic studies also imply that tobacco dependence is affected by polymorphisms in the a3/a5 subunits of the nAChR (CHRNA3/CHRNA5) gene cluster. We, therefore, investigated the impact of two common CHRNA3 polymorphisms (rs1051730/rs1317286) on PPI, startle reactivity, and habituation of the ASR in two independent samples of 107 healthy British volunteers and 73 schizophrenia patients hailing from Germany. In both samples, PPI was influenced by both CHRNA3 polymorphisms (combined p-value ¼ 0.0027), which were strongly linked. Moreover, CHRNA3 genotype was associated with chronicity, treatment, and negative symptoms in the schizophrenia sample. These results suggest that sensorimotor gating is influenced by variations of the CHRNA3 gene, which might also have an impact on the course and severity of schizophrenia.

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Section: Discussionmentioning

confidence: 76%

Sensorimotor Gating is Associated with CHRNA3 Polymorphisms in Schizophrenia and Healthy Volunteers

Petrovsky

Quednow

Ettinger

et al. 2010

Neuropsychopharmacol

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“…For PPI, effects of genotype, trial, and drug treatment were analyzed. In addition, Pearson's product moment correlations were conducted to determine if there was an interrelation between startle magnitude and %PPI, as described previously (Quednow et al, 2006). In biochemical experiments, balanced groups of animals were raised at different times and killed on different days.…”

Section: Discussionmentioning

confidence: 99%

Constitutive Activation of Gαs within Forebrain Neurons Causes Deficits in Sensorimotor Gating Because of PKA-Dependent Decreases in cAMP

Kelly

Isiegas

Cheung

et al. 2006

Neuropsychopharmacol

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Sensorimotor gating, the ability to automatically filter sensory information, is deficient in a number of psychiatric disorders, yet little is known of the biochemical mechanisms underlying this critical neural process. Previously, we reported that mice expressing a constitutively active isoform of the G-protein subunit Gas (Gas*) within forebrain neurons exhibit decreased gating, as measured by prepulse inhibition of acoustic startle (PPI). Here, to elucidate the biochemistry regulating sensorimotor gating and to identify novel therapeutic targets, we test the hypothesis that Gas* causes PPI deficits via brain region-specific changes in cyclic AMP (cAMP) signaling. As predicted from its ability to stimulate adenylyl cyclase, we find here that Gas* increases cAMP levels in the striatum. Suprisingly, however, Gas* mice exhibit reduced cAMP levels in the cortex and hippocampus because of increased cAMP phosphodiesterase (cPDE) activity. It is this decrease in cAMP that appears to mediate the effect of Gas* on PPI because Rp-cAMPS decreases PPI in C57BL/ 6J mice. Furthermore, the antipsychotic haloperidol increases both PPI and cAMP levels specifically in Gas* mice and the cPDE inhibitor rolipram also rescues PPI deficits of Gas* mice. Finally, to block potentially the pathway that leads to cPDE upregulation in Gas* mice, we coexpressed the R(AB) transgene (a dominant-negative regulatory subunit of protein kinase A (PKA)), which fully rescues the reductions in PPI and cAMP caused by Gas*. We conclude that expression of Gas* within forebrain neurons causes PPI deficits because of a PKAdependent decrease in cAMP and suggest that cAMP PDE inhibitors may exhibit antipsychotic-like therapeutic effects.

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“…The entire test session lasted approximately 20 min. Trial exclusion and scoring criteria were identical to those used in previous studies (Quednow et al 2006a;Quednow et al 2006b). Subjects with response rejections >50% were excluded from data analysis.…”

Section: Startle Response Measurementmentioning

confidence: 99%

“…The mean percent PPI of startle magnitude was calculated using the formula [% PPI = 100 × (magnitude on pulse alone (PA) trialsmagnitude on prepulse (PP) trials)/magnitude on PA trials] (Quednow et al 2006a;Quednow et al 2006b). For the assessment of startle habituation, PA trials were divided each into four blocks.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…For the assessment of startle habituation, PA trials were divided each into four blocks. PA trials from the first, second, and third block were taken to calculate PPI (Quednow et al 2006a All demographic data and psychophysiological parameters were analyzed by analysis of variance (ANOVA) with the exception of frequency data. Frequency data were analyzed using χ² tests.…”

Section: Statistical Analysesmentioning

confidence: 99%

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

et al. 2013

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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) 3-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 3-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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Attenuation of the prepulse inhibition of the acoustic startle response within and between sessions

Cited by 34 publications

References 42 publications

Sensorimotor Gating is Associated with CHRNA3 Polymorphisms in Schizophrenia and Healthy Volunteers

Sensorimotor Gating is Associated with CHRNA3 Polymorphisms in Schizophrenia and Healthy Volunteers

Constitutive Activation of Gαs within Forebrain Neurons Causes Deficits in Sensorimotor Gating Because of PKA-Dependent Decreases in cAMP

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

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