It is considered that functional deficiency of the
NMDA receptors in the prefrontal cortex (PFC) is one of the causes of the
cognitive impairment observed in
schizophrenia. As non-human primates display more developed PFC than rodents, they are considered to be useful experimental animals for improving the predictive validity of models used to discover new drugs for treating
cognitive dysfunction. The aim of this study was to develop a convenient model of the
cognitive impairment observed in
schizophrenia using common marmosets and the CANTAB system and to test whether a full agonist of the
dopamine D1 receptor (SKF-81297) was effective against the
cognitive impairment induced in this model. We administered the
NMDA receptor antagonist
ketamine (1.5-16mg/kg, i.m.) to the marmosets to induce
cognitive impairment and then evaluated their working memory function using the CANTAB spatial working memory (SWM) test. The marmosets' working memory was impaired by subanesthetic doses of
ketamine. Next, we tested the effect of
SKF-81297 (3 or 10mg/kg, p.o.) on this
ketamine-induced
cognitive dysfunction. The marmosets were administered
SKF-81297 30min before the
ketamine injection. Pretreatment with
SKF-81297 reversed the
ketamine-induced cognitive deficiency. In this study, we found that a D1 receptor agonist, which has been reported to enhance cognitive function, reversed
ketamine-induced
cognitive impairment in marmosets, which suggests that our marmoset model could be a useful tool for predicting the clinical efficacy of cognitive-enhancing drugs.