Potentiation of cognitive enhancer effects of Alzheimer’s disease medication memantine by alpha7 nicotinic acetylcholine receptor agonist PHA-543613 in the Morris water maze task

Abstract

Rationale There are controversial pieces of evidence whether combination therapies using memantine and cholinesterase inhibitors are beneficial over their monotreatments. However, results of preclinical studies are promising when memantine is combined with agonists and allosteric modulators of the alpha7 nicotinic acetylcholine receptor (nAChR). Objectives Here, we tested the hypothesis that cognitive enhancer effects of memantine can be potentiated through modulating alpha7 nAChRs in a scopolamine-induced amnesia model. Methods Monotreatments, as well as co-administrations of selective alpha7 nicotinic acetylcholine receptor agonist PHA-543613 and memantine were tested in the Morris water maze task in rats. The efficacy of the co-administration treatment was observed on different domains of spatial episodic memory. Results Low dose of memantine (0.1 mg/kg) and PHA-543613 (0.3 mg/kg) successfully reversed scopolamine-induced short-term memory deficits both in monotreatments and in co-administration. When recall of information from long-term memory was tested, pharmacological effects caused by co-administration of subeffective doses of memantine and PHA-543613 exceeded that of their monotreatments. Conclusion Our results further support the evidence of beneficial interactions between memantine and alpha7 nAChR ligands and suggest a prominent role of alpha7 nAChRs in the procognitive effects of memantine.

The effects of bilateral prostriata lesions on spatial learning and memory in the rat

“…Although the interaction is not significant and this may suggest that the trend over days did not differ significantly by group, our results from the sixth day (the platform was removed) show that experiment group stayed on the original platform region for less time compared to other two groups ( Figure 5D ), suggesting at least the trend of the deficits in learning and memory over days. Finally, using the first 2 days as short-term memory practice ( Bruszt et al, 2021 ), we found that the short-term spatial memory in the experimental group was not significantly affected ( Figure 5B ).…”

“…We conducted escape training for each group for 5 days and found that the rats in all groups succeeded in finding the platform, suggesting the acquisition of spatial learning by the end of the training period even in the experiment group. However, when we took the first 2 days as short-term memory practice and the last 2 days as long-term memory one ( Bruszt et al, 2021 ), we found that the short-term spatial memory in the experimental group was not significantly affected while the long-term spatial memory ability changed ( Figure 5B ). These results indicate that it is difficult for the rats in the experimental group to find the platform area on later days even they can find the platform area on the first day.…”

Electroacupuncture Ameliorates Tibial Fracture-Induced Cognitive Dysfunction by Elevating α7nAChR Expression and Suppressing Mast Cell Degranulation in the Hippocampus of Rats

“…PHA-543613 is a selective α 7nAChR agonist. A previous study demonstrated that pretreatment with PHA-543613 successfully reversed scopolamine-induced cognitive decline [ 12 ]. These findings suggested that cholinergic dysfunction is a pathogenic mechanism underlying POCD, which was in agreement with our findings that hippocampal α 7nAChR protein levels were reduced in rats following tibial fracture surgery on days 1 and 3.…”

“…Activation of α 7nAChR exerts significant anti-inflammatory effects on neuroinflammation. α 7nAChR reduces neuroinflammation, thereby serving as a potential therapeutic target [ 11 , 12 ].…”

Anti-Inflammatory Activity of 4-(4-(Heptyloxy)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one via Repression of MAPK/NF-κB Signaling Pathways in β-Amyloid-Induced Alzheimer’s Disease Models

“…The MWM test was carried out under protocols detailed in previous reports [ 55 ]. The test was conducted to assess learning and memory performance.…”