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

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.

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.

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.

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.

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