PD168077, a D4 receptor agonist, reverses object recognition deficits in rats: potential role for D4 receptor mechanisms in improving cognitive dysfunction in schizophrenia

This study investigated the effects of the dopamine D-4 receptor agonist, PD168077, on recognition memory using a novel object recognition task, which detects disruption and improvement of recognition memory in rats by measuring their ability to discriminate between familiar and novel objects. When acquisition and test were 6 h apart (experiment 1), control rats failed to discriminate between familiar and novel objects at test. Rats given low doses of PD168077 (0.3; 1.0 mg/kg) also failed to discriminate between the objects, while rats given higher doses (3.0; 10.0 mg/kg) explored the novel object more than the familiar object, indicating retained memory of the familiar object. Thus, at higher doses, PD168077 improved recognition memory in rats. Experiment 2 tested whether PD168077 would attenuate deficits in novel object recognition induced by sub-chronic phencyclidine. Testing was 1 min after acquisition, such that vehicle pre-treated rats differentiated between the novel and familiar objects: however, sub-chronic phencyclidine-treated rats failed to discriminate between the two, indicating disruption of recognition memory. PD168077 (10 mg/kg) restored the ability of phencyclidine-treated rats to differentiate between the novel and familiar objects, indicating improved recognition memory. The results suggest that D-4 receptor activation can improve cognitive dysfunction in an animal model relevant to schizophrenia.