期刊
BEHAVIOURAL BRAIN RESEARCH
卷 201, 期 2, 页码 325-331出版社
ELSEVIER
DOI: 10.1016/j.bbr.2009.03.013
关键词
Kynurenic acid; Schizophrenia; Rat; Learning; Memory
资金
- NARSAD Young Investigator Award
- National Institute of Mental Health [MH073304, MH066941, MH069670]
The glia-derived molecule kynurenic acid (KYNA) is an antagonist of alpha 7 nicotinic acetylcholine receptors and the glycine(B) binding site on NMDA receptors. KYNA levels are elevated in the brain and cerebrospinal fluid of persons with schizophrenia and Alzheimer's disease, both of which are characterized by deficits in contextual learning and memory. The present study tested the hypothesis that increases in KYNA concentration would impair contextual fear conditioning but spare cue-specific fear conditioning. Rats in each experiment received injections of vehicle solution or 1-kynurenine (L-KYN, 100 mg/kg), the precursor for KYNA. Administration of L-KYN has been shown to produce clinically relevant increases in KYNA concentration. In Experiment 1, L-KYN-treated rats exhibited impaired contextual fear memory compared to control rats, while fear conditioning to a discrete auditory cue was unaffected. In Experiment 2, rats were trained to discriminate between two different training environments, one in which foot shock was delivered and one that was not paired with foot shock. Although both groups of rats eventually learned the discrimination, learning was slower in L-KYN-treated rats. The results of Experiment 3 demonstrated that the deficits in context discrimination could not be explained by the preferential use of an elemental learning strategy by L-KYN-treated rats. Together, these findings indicate that elevated concentration of endogenous KYNA interferes with contextual learning and memory and support the notion that increased concentration of KYNA may contribute to cognitive dysfunction. In addition, these data provide new insight into how novel 'gliotransmitters' may modulate neuronal function and behavior. (C) 2009 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据