title: Comparison of phencyclidine-induced spatial learning and memory deficits and reversal by sertindole and risperidone between Lister Hooded and Wistar rats.
abstract: Visual learning and memory are one of the key cognitive domains disturbed in schizophrenia. Glutamate NMDA receptors play a crucial role in spatial learning and memory and NMDA receptor antagonists, such as phencyclidine (PCP), impair spatial learning and memory. Pigmented rat strains have superior vision than albino rat strains and are therefore commonly used in visually-demanding cognitive tests. However, all previous water maze experiments using acutely administered PCP to induce schizophrenia-like cognitive deficits have been conducted with albino Wistar rats. This study was designed to assess whether pigmented Lister Hooded (LH) rats would be more suitable in modeling acute PCP-induced deficits in Morris water maze (MWM) task than Wistar rats. We also evaluated whether the efficacy of atypical antipsychotics in reversing PCP-induced spatial navigation deficits was dependent on the rat strain. First, we compared the PCP dose-response in the range of 1.3-2.0mg/kg (s.c.) at causing deficits in MWM performance. Then, the efficacies of sertindole 1.6mg/kg (s.c.) and risperidone 0.04mg/kg (s.c.) in reversing PCP-induced spatial navigation deficits were investigated. Drug-naïve LH rats showed a better spatial memory than Wistar rats. Furthermore, PCP induced deficits in spatial navigation at lower doses in LH than in Wistar rats. In addition, PCP-induced deficits were partly reversed by sertindole in LH but not in Wistar rats. Our results suggest that the deficits in spatial learning and memory that resemble memory deficits found in schizophrenia patients are better modeled by PCP in LH rats than Wistar rats.
authors.affiliation: School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland. Electronic address: jouni.ihalainen@uef.fi.
authors.forename: Jouni
authors.initials: J
authors.lastname: Ihalainen
authors.affiliation: School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Katja
authors.initials: K
authors.lastname: Savolainen
authors.affiliation: A.I. Virtanen Institute, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland; Department of Neurology, Kuopio University Hospital, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
authors.affiliation: School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Forsberg
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000633:toxicity; D007093:Imidazoles / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D010622:Phencyclidine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000627:therapeutic use*; D065853:Spatial Learning / Q000187:drug effects; D065854:Spatial Navigation / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D006213:Hallucinogens; D007093:Imidazoles; D007211:Indoles; C066304:sertindole; D010622:Phencyclidine; D018967:Risperidone
keywords: Antipsychotics; Phencyclidine; Rat strain; Schizophrenia; Spatial learning and memory; Water maze