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Biperiden selectively induces memory impairment in healthy volunteers: no interaction with citalopram

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Abstract

Rationale

Traditionally, the non-selective muscarinic antagonist scopolamine has been used to induce episodic memory impairments as found in Alzheimer’s disease (AD). However, it also impairs attention and induces drowsiness. Muscarinic antagonists more selective for the M1 receptor might, therefore, be preferred.

Objectives

We examined the effects of the M1 antagonist biperiden on cognitive functions in order to test the specificity of this drug on memory performance. Additionally, we assessed whether the selective serotonin re-uptake inhibitor citalopram can reverse a possible biperiden-induced impairment.

Methods

The study was conducted according to a double-blind, placebo-controlled, four-way cross-over design. Sixteen volunteers received biperiden (2 mg), citalopram (20 mg), a combination of the two, or a placebo in counterbalanced order with a washout of at least 4 days. Cognitive tests (verbal memory, continuous recognition memory, spatial memory, choice reaction) were performed 4 and 1 h after treatment with citalopram and biperiden, respectively.

Results

Biperiden impaired memory performance in the verbal learning task, the continuous recognition memory test, and the spatial memory task. Effects on attention and side effects, as measured using the choice reaction time test and questionnaires respectively, could be neglected. Citalopram did not affect any of the memory or attention measures taken. Most importantly, citalopram was also unable to reverse the biperiden-induced memory impairments.

Conclusions

Our results, thus, show that the M1 antagonist biperiden may serve as a translational model to induce episodic memory deficits as seen in AD. However, the interactive influence of acetylcholine and serotonin on memory could not be confirmed.

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Acknowledgments

We would like to thank Eini Knuutinen for her assistance in data acquisition. This study was sponsored by the Netherlands Organization for Scientific Research, grant number 451-07-011.

Conflict of interest

Wim J. Riedel was also employed by Cambridge Cognition Ltd., Cambridge, UK, while remaining affiliated to Maastricht University, during the last few years. This raises no conflict of interest. There were no commercial or financial relationships that could be construed as a potential conflict of interest.

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Authors and Affiliations

  1. Faculty of Psychology and Neuroscience, Department of Neuropsychology and Psychopharmacology, Maastricht University, Universiteitssingel 40, 6229 ER, Maastricht, The Netherlands

    Anke Sambeth, Wim J. Riedel, Inge Klinkenberg & Arjan Blokland

  2. BioMag Laboratory, HUS Medical Imaging Center, Helsinki University Central Hospital, PO Box 340, Helsinki, 00029, Finland

    Anke Sambeth & Seppo Kähkönen

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  1. Anke Sambeth
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  2. Wim J. Riedel
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  3. Inge Klinkenberg
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  4. Seppo Kähkönen
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  5. Arjan Blokland
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Correspondence to Anke Sambeth.

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Sambeth, A., Riedel, W.J., Klinkenberg, I. et al. Biperiden selectively induces memory impairment in healthy volunteers: no interaction with citalopram. Psychopharmacology 232, 1887–1897 (2015). https://doi.org/10.1007/s00213-014-3822-9

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  • DOI: https://doi.org/10.1007/s00213-014-3822-9

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