Chemogenetics is a newly developed set of tools that allow for selective manipulation of cell activity. They consist of a receptor mutated irresponsive to endogenous ligands and a synthetic ligand that does not interact with the wild-type receptors. Many different types of these receptors and their respective ligands for inhibiting or excitating neuronal subpopulations were designed in the past few decades. It has been mainly the G-protein coupled receptors (GPCRs) selectively responding to clozapine-N-oxide (CNO), namely Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), that have been employed in research. Chemogenetics offers great possibilities since the activity of the receptors is reversible, inducible on demand by the ligand, and non-invasive. Also, specific groups or types of neurons can be selectively manipulated thanks to the delivery by viral vectors. The effect of the chemogenetic receptors on neurons lasts longer, and even chronic activation can be achieved. That can be useful for behavioral testing. The great advantage of chemogenetic tools is especially apparent in research on brain diseases since they can manipulate whole neuronal circuits and connections between different brain areas. Many psychiatric or other brain diseases revolve around the dysfunction of specific brain networks. Therefore, chemogenetics presents a powerful tool for investigating the underlying mechanisms causing the disease and revealing the link between the circuit dysfunction and the behavioral or cognitive symptoms observed in patients. It could also contribute to the development of more effective treatments.

• MeSH
• duševní poruchy * genetika   metabolismus   MeSH
• klozapin analogy a deriváty   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• neurony metabolismus   účinky léků   MeSH
• nové syntetické drogy farmakologie   MeSH
• receptory spřažené s G-proteiny metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• klozapin MeSH
• nové syntetické drogy MeSH
• receptory spřažené s G-proteiny MeSH

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