title: The combination of memantine and galantamine improves cognition in rats: The synergistic role of the α7 nicotinic acetylcholine and NMDA receptors.
abstract: The combination of memantine and acetylcholinesterase inhibitors (AChEIs) is used as a therapeutic strategy to improve cognition in Alzheimer's disease. Among AChEIs, galantamine, which is also a positive allosteric modulator (PAM) of nicotinic acetylcholine receptors (nAChRs), including α7-nAChRs, may be particularly beneficial. The α7-nAChR is involved in interactions between the cholinergic and glutamatergic systems. In the present study, we investigated the potential role of α7-nAChRs in the pro-cognitive effects of this drug combination. To this aim, cognitive performance in rats was assessed using the attentional set shifting task (ASST) and novel object recognition task (NORT). Co-administration of inactive doses of memantine with galantamine facilitated the rats' set-shifting performance and reversed delay-induced deficits in object recognition. These effects were blocked by the α7-nAChR antagonist methyllycaconitine, suggesting that the observed cognitive enhancement is α7-nAChR dependent. Moreover, combined administration of memantine with inactive doses of selective α7-nAChRs PAMs, CCMI and PNU-120596, also improved ASST and NORT performance in a methyllycaconitine-dependent manner. Stimulation of α7-nAChRs may underlie the pro-cognitive effects of combining memantine and galantamine. Our results suggest that memantine, when given with enhancers of α7-nAChRs, may represent an effective strategy for cognitive improvement.
authors.affiliation: Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. Electronic address: nikifor@if-pan.krakow.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Nikiforuk
authors.affiliation: Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Potasiewicz
authors.affiliation: Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kos
authors.affiliation: Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Popik
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D005702:Galantamine / Q000494:pharmacology*; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D002800:Cholinesterase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005702:Galantamine; D008559:Memantine
keywords: Animal models; Cognition; Galantamine; Memantine; Positive allosteric modulators; α-7 Nicotinic receptor