title: 3-Furan-2-yl-N-p-tolyl-acrylamide, a positive allosteric modulator of the α7 nicotinic receptor, reverses schizophrenia-like cognitive and social deficits in rats.
abstract: The cognitive impairments and negative symptoms experienced by schizophrenia patients still await effective treatment. Alpha7 nicotinic acetylcholine receptors (α7 nAChRs) have gain considerable attention in this regard. It has been recently proposed that positive allosteric modulators (PAMs) of α7 nAChRs may represent an alternative strategy to that based on orthosteric agonists. The aim of the present study is to evaluate the efficacy of PAM-2 (3-furan-2-yl-N-p-tolyl-acrylamide) against cognitive deficits and negative-like symptoms in a rat model of schizophrenia based on administration of ketamine, a NMDAR antagonist. The activity of PAM-2 was compared to that elicited by DMXBA, an α7 nAChR partial agonist. For this purpose, the attentional set-shifting task (ASST) and the novel object recognition task (NORT) were used. The efficacies of PAM-2 and DMXBA against ketamine-induced social withdrawal were assessed using the social interaction test (SIT). The results demonstrated that PAM-2 and DMXBA ameliorated ketamine-induced cognitive impairments on the ASST and NORT as well as produced pro-social activities in the SIT. Moreover, the co-administration of inactive doses of PAM-2 and antipsychotic drugs, clozapine or risperidone, reversed ketamine-induced deficits. The present findings provide further support for the concept that α7-PAMs could be used either alone or in combination with antipsychotics for schizophrenia therapy.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, 31-343 Kraków, Smętna street 12, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Potasiewicz
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, 31-343 Kraków, Smętna street 12, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Hołuj
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, 31-343 Kraków, Smętna street 12, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kos
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, 31-343 Kraków, Smętna street 12, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Popik
authors.affiliation: Department of Medical Education, California Northstate University College of Medicine, CA 95757, USA.
authors.forename: Hugo R
authors.initials: HR
authors.lastname: Arias
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Department of Behavioral Neuroscience and Drug Development, 31-343 Kraków, Smętna street 12, Poland. Electronic address: nikifor@if-pan.krakow.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Nikiforuk
mesh_terms: D000178:Acrylamides / Q000008:administration & dosage* / Q000627:therapeutic use; D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001288:Attention / Q000187:drug effects; D001597:Benzylidene Compounds / Q000008:administration & dosage; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D005663:Furans / Q000008:administration & dosage* / Q000627:therapeutic use; D007649:Ketamine / Q000008:administration & dosage; D008297:Male; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D021641:Recognition, Psychology / Q000187:drug effects; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D012565:Schizophrenic Psychology; D012919:Social Behavior; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: C000593312:3-furan-2-yl-N-p-tolylacrylamide; D000178:Acrylamides; D014150:Antipsychotic Agents; D001597:Benzylidene Compounds; D005663:Furans; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; D064569:alpha7 Nicotinic Acetylcholine Receptor; D007649:Ketamine; C088936:3-(2,4-dimethoxybenzylidene)anabaseine
keywords: Animal model of schizophrenia; Antipsychotics; Cognitive flexibility; Positive allosteric modulator; Recognition memory; α7 Nicotinic acetylcholine receptors