Differential effects of iloperidone, clozapine, and haloperidol on working memory of rats in the delayed non-matching-to-position paradigm.
BACKGROUND
Because cognitive function, particularly working memory (WM), is severely impaired in schizophrenia, evaluation of neuroleptic medication should include investigation of possible effects on cognition. Iloperidone is a promising, novel atypical neuroleptic drug (NL), for which no cognitive data is presently available.


OBJECTIVE
To investigate whether the novel atypical NL iloperidone would affect performance of rats on a WM test, using a delayed non-matching-to-position (DNMTP) paradigm, and compare its effects with those of the atypical NL clozapine and the typical NL haloperidol.


METHODS
Male Lister Hooded rats trained to criterion in an operant DNMTP task (0-64 s delay intervals) were administered vehicle, iloperidone (0.03, 0.1 mg/kg, i.p.), clozapine (0.1, 0.3 mg/kg, s.c.), haloperidol (0.003, 0.01, 0.03 mg/kg, s.c.), or scopolamine (0.05 mg/kg, s.c.). Together with choice accuracy, the motor performance of the task was measured.


RESULTS
It was found that: (1) iloperidone significantly improved choice accuracy delay-dependently while impairing task performance; (2) the atypical NL clozapine had no effect on choice accuracy and parameters related to motor function, but significantly increased the number of uncompleted trials; (3) haloperidol did not affect choice accuracy except at the longest delay with the highest dose, but in contrast to clozapine it significantly impaired task performance.


CONCLUSIONS
In accordance with their different pharmacological profiles, the three NLs iloperidone, clozapine, and haloperidol have different effects in this preclinical cognitive task. These results might provide important information for the development of NLs with beneficial effects on cognition.
Gemperle
Angela Y
AY
Nervous System Department, Novartis Pharma Inc., 4002, Basel, Switzerland.
McAllister
Kevin H
KH
Olpe
Hans-Rudolf
HR
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009666:Nose / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011930:Reaction Time; D012601:Scopolamine / Q000494:pharmacology; D013997:Time Factors
D014150:Antipsychotic Agents; D007555:Isoxazoles; D018727:Muscarinic Antagonists; D010880:Piperidines; D012601:Scopolamine; D003024:Clozapine; D006220:Haloperidol; C081732:iloperidone