The nicotinic ¦Á7 receptor agonist GTS-21 improves cognitive performance in?ketamine impaired rhesus monkeys

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• 作者：Christopher E. Cannon ; Vanita Puri ; Jeffrey A. Vivian ; Melissa S. Egbertson ; Donnie Eddins ; Jason M. Uslaner
• 关键词：Schizophrenia ; Prefrontal cortex ; GTS-21 ; Primate ; Nicotinic ¦Á7 receptor ; Donepezil ; Cognition
• 刊名：Neuropharmacology
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：64
• 期：Complete
• 页码：191-196
• 全文大小：352 K

文摘

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 ¦Á7 agonist GTS-21 (0.03?mg/kg) significantly attenuated the ketamine-induced impairment, consistent with reports from clinical trials suggesting that nicotinic ¦Á7 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¡¯.