title: Improvement of ketamine-induced social withdrawal in rats: the role of 5-HT7 receptors.
abstract: Social withdrawal, one of the core negative symptoms of schizophrenia, can be modelled in the social interaction (SI) test in rats using N-methyl-D-aspartate receptor glutamate receptor antagonists. We have recently shown that amisulpride, an antipsychotic with a high affinity for serotonin 5-HT7 receptors, reversed ketamine-induced SI deficits in rats. The aim of the present study was to further elucidate the potential involvement of 5-HT7 receptors in the prosocial action of amisulpride. Acute administration of amisulpride (3 mg/kg) and SB-269970 (1 mg/kg), a 5-HT7 receptor antagonist, reversed ketamine-induced social withdrawal, whereas sulpiride (20 or 30 mg/kg) and haloperidol (0.2 mg/kg) were ineffective. The 5-HT7 receptor agonist AS19 (10 mg/kg) abolished the prosocial efficacy of amisulpride (3 mg/kg). The coadministration of an inactive dose of SB-269970 (0.2 mg/kg) showed the prosocial effects of inactive doses of amisulpride (1 mg/kg) and sulpiride (20 mg/kg). The anxiolytic chlordiazepoxide (2.5 mg/kg) and the antidepressant fluoxetine (2.5 mg/kg) were ineffective in reversing ketamine-induced SI deficits. The present study suggests that the antagonism of 5-HT7 receptors may contribute towards the mechanisms underlying the prosocial action of amisulpride. These results may have therapeutic implications for the treatment of negative symptoms in schizophrenia and other disorders characterized by social withdrawal.
authors.affiliation: Department of Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Hołuj
authors.forename: Piotr
authors.initials: P
authors.lastname: Popik
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Nikiforuk
mesh_terms: D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D010636:Phenols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin / Q000378:metabolism*; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D012920:Social Behavior Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D010636:Phenols; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D007649:Ketamine; D013469:Sulpiride; D000077582:Amisulpride