title: Amisulpride promotes cognitive flexibility in rats: the role of 5-HT7 receptors.
abstract: The antagonism of 5-HT7 receptors may contribute to the antidepressant and procognitive actions of the atypical antipsychotic drug, amisulpride. It has been previously demonstrated that the selective 5-HT7 receptor antagonist reversed restraint stress-induced cognitive impairments in a rat model of frontal-dependent attentional set-shifting task (ASST). Therefore, the first aim of the present study was to assess the effectiveness of amisulpride against stress-evoked cognitive inflexibility. The second goal was to elucidate whether the pro-cognitive effect of amisulpride could be due to the compound's action at 5-HT7 receptors. Rats repeatedly exposed (1 h daily for 7 days) to restraint stress demonstrated impaired performance on the extra-dimensional (ED) set-shifting stage of the ASST. Amisulpride (3 mg/kg) given to stressed rats 30 min before testing reversed this restraint-induced cognitive inflexibility and improved ED performance of the unstressed control group. The 5-HT7 receptor agonist, AS19 (10 mg/kg), abolished the pro-cognitive efficacy of amisulpride (3 mg/kg). The present study suggests that the antagonism of 5-HT7 receptors may contribute to the mechanisms underlining the pro-cognitive action of amisulpride. These results may have therapeutic implications in frontal-like deficits associated with stress-related disorders.
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: Piotr
authors.initials: P
authors.lastname: Popik
mesh_terms: D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001288:Attention / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy*; D004195:Disease Models, Animal; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: C505862:AS 19 compound; D014150:Antipsychotic Agents; D011720:Pyrazoles; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C104425:serotonin 7 receptor; D013469:Sulpiride; D000077582:Amisulpride