Modelling Alzheimer-like cognitive deficits in rats using biperiden as putative cognition impairer

Abstract

To enable the development of effective treatments for dementias such as Alzheimer's disease (AD), it is important to establish valid animal models of cognitive impairments. Scopolamine is widely used to induce cognitive deficits in animal models of AD, but also causes non-cognitive side effects. We assessed whether biperiden, a selective antagonist of M1 muscarinic receptors, which are predominantly expressed in brain areas involved in cognitive processes, causes cognitive deficits without inducing peripheral side-effects. Two different doses of biperiden (3 or 10mgkg−1) on the acquisition of a spatial cone field task were assessed in male Lister Hooded rats. This task measures, among others, spatial working (WM) – and reference memory (RM) simultaneously. Biperiden did not impair learning of the task. The animals reached asymptotic levels for all variables except reference memory and the number of rewards collected. However, the 10mgkg−1 dose decreased the tendency of rats to use searching strategies to solve the task and made them slower to start searching and completing the task. In conclusion, though no effects on WM and RM performance were seen, the present study cannot conclude that biperiden acts as a more selective cognition impairer than scopolamine in other rats strains and/or other doses than those tested.