A preliminary investigation into the effects of antipsychotics on sub-chronic phencyclidine-induced deficits in attentional set-shifting in female rats.
BACKGROUND
The NMDA receptor antagonist, phencyclidine (PCP), has been shown to induce symptoms characteristic of schizophrenia. A loss in executive function and the ability to shift attention between stimulus dimensions is impaired in schizophrenia; this can be assessed in rodents by the perceptual attentional set-shifting task.


OBJECTIVE
The aim of this study was to investigate whether the deficits induced by sub-chronic PCP in attentional set-shifting could be reversed by sub-chronic administration of clozapine, risperidone or haloperidol.


METHODS
Adult female hooded-Lister rats received sub-chronic PCP (2 mg/kg) or vehicle (1 ml/kg) i.p. twice daily for 7 days, followed by a 7-day washout period. PCP-treated rats then received clozapine, risperidone, haloperidol or vehicle once daily for 7 days and were then tested in the perceptual set-shifting task.


RESULTS
PCP significantly (p<0.01) increased the number of trials to reach criterion in the EDS phase when compared to vehicle and this deficit was significantly (p<0.01) attenuated by sub-chronic clozapine (2.5 mg/kg) and risperidone (0.2 mg/kg), but not by sub-chronic haloperidol treatment (0.05 mg/kg).


CONCLUSIONS
These data show that sub-chronic PCP produced a robust deficit within the EDS phase in the attentional set-shifting task, in female rats. Atypical antipsychotics, clozapine and risperidone, but not the classical agent, haloperidol, significantly improved the PCP-induced cognitive deficit.
McLean
Samantha L
SL
Bradford School of Pharmacy, The University of Bradford, Bradford, West Yorkshire BD7 1DP, UK.
Beck
Jonathan P
JP
Woolley
Marie L
ML
Neill
Joanna C
JC
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005260:Female; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D010622:Phencyclidine / Q000008:administration & dosage*; D010865:Pilot Projects; D051381:Rats; D011919:Rats, Inbred Strains; D018967:Risperidone / Q000494:pharmacology; D012718:Set, Psychology; D012737:Sex Factors; D018709:Statistics, Nonparametric
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D010622:Phencyclidine; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone