Clozapine but not haloperidol treatment reverses sub-chronic phencyclidine-induced disruption of conditional discrimination performance

Abstract

Abusers of phencyclidine (PCP) often present with a symptom profile similar to that exhibited by schizophrenic patients. Animal models utilising such psychotomimetics are currently informing research into the condition. Accumulating evidence suggests that a central cognitive deficit in schizophrenia is the inability to use task-setting cues to guide goal directed behaviour and that this ability is mediated by prefrontal dopamine (DA). The current study used the non-competitive NMDA antagonist phencyclidine (PCP) and Haloperidol (typical antipsychotic) and Clozapine (atypical antipsychotic) in order to further investigate the influence of DAergic manipulation on a task that requires the use of conditional information to inform goal-directed performance. An instrumental conditional discrimination task was employed in which rats learn to respond appropriately according to the presence of specific auditory conditional stimuli. Probe test 1 showed impaired conditional discrimination performance following sub-chronic PCP administration (seven twice-daily injection protocol) compared to control which was reversed by acute treatment with clozapine (5 mg/kg) but not haloperidol (0.1 mg/kg) both administered 60 min pre-test. Probe test 2 (8 days post-treatment) showed enduring deficits to conditional discrimination performance that were again reversed by clozapine but not haloperidol (injection procedures as above). These results show that tasks dependent upon conditional relationships…