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The PDE5 inhibitor vardenafil does not affect auditory sensory gating in rats and humans

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Abstract

Rationale

Sensory gating is an adaptive mechanism of the brain to prevent overstimulation. Patients suffering from clinical disorders such as Alzheimer’s disease or schizophrenia exhibit a deficit in gating, which indicates not only an impairment in basic information processing that might contribute to the cognitive problems seen in these patients. Phosphodiesterase type 5 inhibitors (PDE5-Is) have been shown to improve cognition in rodents in various behavioural tasks and might consequently be an interesting target for cognition enhancement. However, the effects of PDE5-Is on sensory gating are not known yet.

Objectives

This work aims to study the effects of PDE5 inhibition on auditory sensory gating in rats and humans.

Methods

In the rat study, vehicle or 0.3–3 mg/kg of the PDE5-I vardenafil was given orally 30 min before testing and electrode locations were the vertex, hippocampus and the striatum. The human subjects received placebo, 10–20 mg vardenafil 85 min before testing and sensory gating was measured at the cortex (Fz, Fcz and Cz) electrodes.

Results

Significant gating was only found for the N1 component in rats while all three peaks P1, N1 and P2 showed gating in humans, i.e. the response to the second sound click was decreased as compared with the first for these deflections. Administration of vardenafil did neither have an effect on sensory gating in rats nor in humans.

Conclusions

These findings imply that positive effects of PDE5 inhibition on cognition are not mediated by more early phases of information processing.

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Authors and Affiliations

  1. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands

    O. A. H. Reneerkens, M. A. Van Duinen, H. W. M. Steinbusch & J. Prickaerts

  2. Department of Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, The Netherlands

    A. Sambeth & A. Blokland

  3. European Graduate School of Neuroscience (EURON), Maastricht University, P.O. Box 616, 6200, MD, Maastricht, The Netherlands

    O. A. H. Reneerkens, A. Sambeth, M. A. Van Duinen, A. Blokland, H. W. M. Steinbusch & J. Prickaerts

Authors
  1. O. A. H. Reneerkens
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  2. A. Sambeth
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  3. M. A. Van Duinen
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  4. A. Blokland
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  5. H. W. M. Steinbusch
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  6. J. Prickaerts
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Correspondence to J. Prickaerts.

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Reneerkens, O.A.H., Sambeth, A., Van Duinen, M.A. et al. The PDE5 inhibitor vardenafil does not affect auditory sensory gating in rats and humans. Psychopharmacology 225, 303–312 (2013). https://doi.org/10.1007/s00213-012-2817-7

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  • DOI: https://doi.org/10.1007/s00213-012-2817-7

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