title: Effects of the selective 5-HT7 receptor antagonist SB-269970 and amisulpride on ketamine-induced schizophrenia-like deficits in rats.
abstract: A wide body of evidence suggests that 5-HT7 receptors are implicated in a variety of central nervous system functions, including control of learning and memory processes. According to recent preclinical data, the selective blockade of these receptors may be a potential target for cognitive improvement in schizophrenia. The first aim of the present study was to evaluate the effects of the selective 5-HT7 receptor antagonist, SB-269970, and the antipsychotic drug with a high affinity for 5-HT7 receptors, amisulpride, on ketamine-induced deficits in attentional set-shifting and novel object recognition tasks in rats. Because the role of 5-HT7 receptor blockade in ameliorating positive and negative symptoms of schizophrenia remains equivocal, the second aim of these experiments was to examine the effectiveness of SB-269970 and amisulpride in reversing ketamine-induced deficits in prepulse inhibition of the startle reflex and in social interaction test in rats. The study revealed that acute administration of SB-269970 (1 mg/kg) or amisulpride (3 mg/kg) ameliorated ketamine-induced cognitive inflexibility and novel object recognition deficit in rats. Both compounds were also effective in attenuating ketamine-evoked disruption of social interactions. In contrast, neither SB-269970 nor amisulpride affected ketamine-disrupted prepulse inhibition or 50 kHz USVs accompanying social behaviour. In conclusion, antagonism of 5-HT7 receptors may represent a useful pharmacological approach in the treatment of cognitive deficits and some negative symptoms of schizophrenia.
authors.affiliation: Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. nikifor@if-pan.krakow.pl
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Nikiforuk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kos
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Fijał
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Hołuj
authors.forename: Dominik
authors.initials: D
authors.lastname: Rafa
authors.forename: Piotr
authors.initials: P
authors.lastname: Popik
mesh_terms: D000077582:Amisulpride; D000818:Animals; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D010636:Phenols / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012559:Schizophrenia / Q000139:chemically induced* / Q000188:drug therapy*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010636:Phenols; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D007649:Ketamine; D013469:Sulpiride; D000077582:Amisulpride