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Mnemonic and behavioral effects of biperiden, an M1-selective antagonist, in the rat

Abstract

Rationale

There is a persistent pressing need for valid animal models of cognitive and mnemonic disruptions (such as seen in Alzheimer’s disease and other dementias) usable for preclinical research.

Objectives

We have set out to test the validity of administration of biperiden, an M1-acetylcholine receptor antagonist with central selectivity, as a potential tool for generating a fast screening model of cognitive impairment, in outbred Wistar rats.

Methods

We used several variants of the Morris water maze task: (1) reversal learning, to assess cognitive flexibility, with probe trials testing memory retention; (2) delayed matching to position (DMP), to evaluate working memory; and (3) “counter-balanced acquisition,” to test for possible anomalies in acquisition learning. We also included a visible platform paradigm to reveal possible sensorimotor and motivational deficits.

Results

A significant effect of biperiden on memory acquisition and retention was found in the counter-balanced acquisition and probe trials of the counter-balanced acquisition and reversal tasks. Strikingly, a less pronounced deficit was observed in the DMP. No effects were revealed in the reversal learning task.

Conclusions

Based on our results, we do not recommend biperiden as a reliable tool for modeling cognitive impairment.

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Notes

  1. While we had also data for the distance required to reach the platform, it correlated strongly with escape latency, r(870) = .94, 95% CI = [.94, .95], p < .001, so we show results only for escape latency for simplicity.

  2. b refers to regression coefficient

Abbreviations

Ach:

Acetylcholine

AChR:

Acetylcholine receptors

AD:

Alzheimer’s disease

BBB:

Blood-brain barrier

BIP:

Biperiden

C:

Control group

CA:

Counter-balanced acquisition

cAMP:

Cyclic adenosine monophosphate

CNS:

Central nervous system

DMP:

Delayed matching to position

DMSO:

Dimethyl-sulfoxide

GABA:

Gamma-amino-butyric acid

GPCRs:

G-Protein coupled receptors

i.p.:

Intraperitoneally

ITI:

Inter-trial interval

mAChR:

Muscarinic acetylcholine receptors

MWM:

Morris water maze

NSP:

Non-spatial pretraining

s.c.:

Subcutaneously

SCOP:

Scopolamine

VP:

Visible platform

References

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Acknowledgements

We thank Michaela Radostna, Barbara Stuchlikova, Vladimira Markova, Antonin Zahalka, and Jindrich Kalvoda for the technical support and assistance.

Funding

This work was supported by GACR grant 17-04047S. Institutional support for IPHYS was provided by RVO: 67985823.

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Authors

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Correspondence to Jan Svoboda or Aleš Stuchlík.

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The authors declare that they have no conflict of interest.

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Popelíková, A., Bahník, Š., Lobellová, V. et al. Mnemonic and behavioral effects of biperiden, an M1-selective antagonist, in the rat. Psychopharmacology 235, 2013–2025 (2018). https://doi.org/10.1007/s00213-018-4899-3

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  • DOI: https://doi.org/10.1007/s00213-018-4899-3

Keywords

  • Anticholinergics
  • Muscarinic receptors
  • Learning
  • Memory
  • Morris water maze
  • Rat