Cannon_2013_Neuropharmacol_64_191

The cognitive deficits associated with schizophrenia are recognized as a core component of the disorder yet there remain no available therapeutics to treat these symptoms of the disease As a result there is a need for establishing predictive preclinical models to identify the therapeutic potential of novel compounds In the present study rhesus monkeys were trained in the object retrieval-detour task which is dependent on the prefrontal cortex a brain region implicated in the cognitive deficits associated with schizophrenia The NMDA receptor antagonist ketamine significantly impaired performance without affecting measures of motor or visuospatial abilities Pre-treatment with the nicotinic alpha7 agonist GTS-21 0.03 mg/kg significantly attenuated the ketamine-induced impairment consistent with reports from clinical trials suggesting that nicotinic alpha7 receptor agonism has pro-cognitive potential in clinical populations In contrast pretreatment with the acetylcholinesterase inhibitor donepezil failed to reverse the ketamine-induced impairment consistent with studies showing a lack of pro-cognitive effects in patients with schizophrenia These data suggest that the ketamine-impaired object retrieval-detour task could provide a model with improved predictive validity for drug development and confirm the need for additional efforts in back-translation This article is part of a Special Issue entitled Cognitive Enhancers'.