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.

• Klíčová slova
• Anticholinergics, Learning, Memory, Morris water maze, Muscarinic receptors, Rat,
• MeSH
• Alzheimerova nemoc psychologie   MeSH
• antagonisté muskarinových receptorů farmakologie   MeSH
• biperiden farmakologie   MeSH
• bludiště - učení účinky léků   MeSH
• chování zvířat účinky léků   MeSH
• kognitivní dysfunkce psychologie   MeSH
• krátkodobá paměť účinky léků   MeSH
• krysa rodu Rattus * MeSH
• modely nemocí na zvířatech * MeSH
• poruchy paměti psychologie   MeSH
• potkani Wistar MeSH
• reverzní učení účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus * MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté muskarinových receptorů MeSH
• biperiden MeSH

Muscarinic acetylcholine receptors (mAChRs) have been found to regulate many diverse functions, ranging from motivation and feeding to spatial navigation, an important and widely studied type of cognitive behavior. Systemic administration of non-selective antagonists of mAChRs, such as scopolamine or atropine, have been found to have adverse effects on a vast majority of place navigation tasks. However, many of these results may be potentially confounded by disruptions of functions other than spatial learning and memory. Although studies with selective antimuscarinics point to mutually opposite effects of M1 and M2 receptors, their particular contribution to spatial cognition is still poorly understood, partly due to a lack of truly selective agents. Furthermore, constitutive knock-outs do not always support results from selective antagonists. For modeling impaired spatial cognition, the scopolamine-induced amnesia model still maintains some limited validity, but there is an apparent need for more targeted approaches such as local intracerebral administration of antagonists, as well as novel techniques such as optogenetics focused on cholinergic neurons and chemogenetics aimed at cells expressing metabotropic mAChRs.

• Klíčová slova
• acetylcholine, behavior, biperiden, learning, memory, receptor, rodents, scopolamine,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH