Browsing by Subject "5-HT6-antagonisti"
Now showing items 1-1 of 1
-
(2011)Literature review: There is a need for new disease modifying therapies for Alzheimer disease. In order to develop these, animal models with better Alzheimer disease pathology are required. Old rat models like giving scopolamine or MK-801 or using aged rats don't have many of the characteristics of Alzheimer disease although they diminish cognitive functions in different models. Newer models like transgenic and Aβ-injected or -infused rats have much more analogy to the pathology of Alzheimer disease - at least when Aβ-pathophysiology is concerned. Taupathophysiology however doesn't occur in either of the models. On the other hand Aβ has a bigger role in the pathophysiology of Alzheimer disease so it's more important to have that in both models. These two models seem to be quite similar in modelling the disease. Injecting or infusing Aβ to the brain of the rat may be easier to conduct in practice than to create a transgenic rat line. However in transgenic rats Aβ-pathophysiology is developed intracellularly like in Alzheimer disease instead of giving aggregated Aβ outside of the brain. Still both of the models can be used as well to study new therapies especially affecting Aβ-pathophysiology. Experimental part: The purpose of the study was to validate elevated plus-maze (EPM) as a cognition model with a Trial1/Trial2-protocol (T1/T2) in mice. In this experiment a-five-minute-trial was used and thus different parameters related to cognition were measured. The memory of the mice was tried to be disrupted with time delay (1-18 d) between trials or with muscarinic receptor antagonist scopolamine (0.1-0.8 mg/kg i.p.) 30 minutes pre-T1. These experiments were conducted in C57BL/6J- and ICR:(CD-1)-mice. The only group in the time interval experiment that had a trend of forgetting was the 18 d group of ICR:(CD-1)-mice. Thus 21 d interval was also studied, but clear signs of forgetting couldn't be seen. Scopolamine didn't disrupt memory in ICR:(CD-1)-mice but in C57BL/6J-mice it did significantly with doses 0.2-0.8 mg/kg. Based on this 0.2 mg/kg was selected to be used in further studies in C57BL/6J-mice. In this model the nootropic effects of donepezile (0.3, 0.8 and 1.5 mg/kg s.c.), memantine (5.0 and 10.0 mg/kg s.c.) and an experimental 5-HT6-antagonist SB742457 (1.5 and 6.0 mg/kg s.c.) were studied. These compounds were allocated 40 minutes pre-T1 and scopolamine 30 minutes pre-T1. Memantine (5.0 mg/kg) clearly and donepezile (1.5 mg/kg) with a strong trend enhanced cognition disrupted by scopolamine. These results suggest that EPM can be used when testing nootropic effects.
Now showing items 1-1 of 1