3¦Á5¦Â-Pregnanolone glutamate, a use-dependent NMDA antagonist, reversed spatial learning deficit in an animal model of schizophrenia

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• 作者：Karel Vales ; Lukas Rambousek ; Kristina Holubova ; Jan Svoboda ; Vera Bubenikova-Valesova ; Hana Chodounska ; Ladislav Vyklicky ; Ales Stuchlik
• 关键词：Schizophrenia-like behavior ; MK-801 ; Use-dependent ; NMDA antagonist ; Anxiety ; Pregnanolone glutamate ; Carousel maze
• 刊名：Behavioural Brain Research
• 出版年：2012
• 出版时间：1 November, 2012
• 年：2012
• 卷：235
• 期：1
• 页码：82-88
• 全文大小：644 K

文摘

Neuroactive steroids modulate receptors for neurotransmitters in the brain and thus might be efficacious in the treatment of various diseases of the central nervous system such as schizophrenia. We have designed and synthetized a novel use-dependent NMDA receptor antagonist 3¦Á5¦Â-pregnanolone glutamate (3¦Á5¦Â-P-Glu). In this study, we evaluate procognitive properties of 3¦Á5¦Â-P-Glu in an animal model of schizophrenia induced by systemic application of MK-801. The procognitive properties were evaluated using active place avoidance on a rotating arena (Carousel maze). We evaluated effects of 3¦Á5¦Â-P-Glu on the avoidance, on locomotor activity, and anxiety. 3¦Á5¦Â-P-Glu alone altered neither spatial learning nor locomotor activity in control animals. In the model animals, 3¦Á5¦Â-P-Glu reversed the MK-801-induced cognitive deficit without reducing hyperlocomotion. The highest dose of 3¦Á5¦Â-P-Glu also showed anxiolytic properties. Taken together, 3¦Á5¦Â-P-Glu may participate in the restoration of normal brain functioning and these results may facilitate the development of new promising drugs improving cognitive functioning in schizophrenia.