Performance of male C57BL/6J mice and Wistar rats in the water maze following various schedules of phencyclidine treatment.

To create an animal model of cognitive deficits seen in schizophrenia, researchers tested various doses and schedules of the drug phencyclidine (PCP) in male mice and rats performing a spatial water maze task. A 10-day pre-treatment period prevented PCP-induced motor problems in mice, while 3 days sufficed for rats. PCP impaired spatial learning only when given before daily training trials, not when given immediately after. The optimal dose for producing cognitive impairment with minimal side effects was 2.5 mg/kg. Results indicate PCP disrupts learning and possibly retrieval but not the consolidation of new information.

Study at a glance

Abstract

In order to establish an animal model of cognitive impairments relevant to schizophrenia, we set out to obtain an optimal treatment protocol with phencyclidine (PCP) that would lead to robust cognitive impairment with minimal PCP-related adverse effects. Effects of various doses (0.63-5 mg/kg), pre-treatment period (0, 3, 7 and 10 days before the beginning of acquisition) and treatment schedules (before the first or immediately after the last trial on each day) of PCP on the performance of male C57BL/6J mice and Wistar rats in the spatial version of the water maze were studied. In mice, a 10-day pre-treatment period was required to prevent PCP-induced motor impairments, whereas a 3-day pre-treatment was sufficient in rats. PCP impaired spatial learning in both rats and mice, if animals were administered PCP prior to the first trial. The optimal dose was 2.5 mg/kg. In contrast, animals given PCP immediately after the daily training sessions performed as well as controls. Thus, PCP impairs spatial learning in the water maze only when present in the organism. It can be concluded that PCP interferes with learning, and perhaps retrieval, but not consolidation of newly acquired information.