We have recently shown impairments in working memory induced by acute phencyclidine (PCP) using a novel object recognition task (Ennaceur and Delacour, 1988) in the rat (Grayson and Neill, 2004). This task may have some relevance for the psychopathology of schizophrenia as working memory is impaired in schizophrenics (Gabrovska et al., 2003). The aim of this study was to assess the ability of typical and atypical antipsychotics to attenuate the PCP-induced impairment in this task.

Subjects were 42 female hooded-Lister rats (220 ± 18g), group housed under standard laboratory conditions and randomly assigned to receive either vehicle (n=10; 0.9% saline twice daily) or PCP (n=32; 2mg/kg twice daily) for seven days. Subsequently, animals were given a 7 day drug-free period prior to antipsychotic treatment. Haloperidol (hal; 0.05 & 0.075mg/kg), clozapine (cloz; 1 & 5mg/kg) or vehicle was administered i.p. 30min prior to testing. Testing consisted of a 3min acquisition phase whereby rats explored two novel objects followed by a 1min inter-trial interval, when objects were changed and rats returned to the home cage. Finally in the retention trial, rats explored a familiar and a novel object for 3min. Object exploration is defined by rats licking, sniffing, or touching the object with forepaws whilst sniffing. The exploration time (s) of each object in each trial was recorded. Data are expressed as the mean ± SEM (n=7-12 per group) and analysed by paired samples t-test.

There was no difference in exploration time (s) of the two familiar objects in the acquisition trial in any treatment group, (table 1). A significant (p<0.05) increase in time (s) spent exploring the novel object was observed in the retention trial in the vehicle control groups. There was no significant difference in the time-spent (s) exploring the familiar and the novel objects in the PCP treated group. Administration of cloz but not hal reversed the impairment induced by sub-chronic PCP treatment, table 1.

Table 1. The ability of hal and cloz to reverse the disruption in short-term working memory induced by sub-chronic PCP treatment. *P<0.05 significant difference from the familiar object.

These results provide support to our earlier work showing that acute PCP induces a robust object recognition deficit (Grayson & Neill, 2004). Furthermore, clozapine but not haloperidol has efficacy to reverse this deficit suggesting that this test may have some validity for cognitive dysfunction associated with schizophrenia.

Ennaceur A and Delacour J, (1988) Behav Brain Res 31:47-59.
Gabrovska et al. (2003) Schizophr Res 59: 277-286.
Grayson B and Neill J.C (2004) J. Psychopharm 18 : A55.