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向大鼠伏隔核内注射针对谷氨酸脱羧酶mRNA的一种亚型GAD65而非GAD67 mRNA的反义寡脱氧核苷酸,会损害大鼠的持续注意力表现。

Intra-accumbens infusions of antisense oligodeoxynucleotides to one isoform of glutamic acid decarboxylase mRNA, GAD65, but not to GAD67 mRNA, impairs sustained attention performance in the rat.

作者信息

Miner L A, Sarter M

机构信息

Department of Psychology, The Ohio State University, 27 Townshend Hall, Columbus, OH 43210, USA.

出版信息

Brain Res Cogn Brain Res. 1999 Jan;7(3):269-83. doi: 10.1016/s0926-6410(98)00030-5.

DOI:10.1016/s0926-6410(98)00030-5
PMID:9838159
Abstract

The effects of bilateral infusions of antisense oligodeoxynucleotides (ODNs) for the two isoforms of glutamic acid decarboxylase (GAD65; GAD67) into the nucleus accumbens on the performance of intact rats in a task designed to assess sustained attention were tested. The task required the animals to discriminate between signal and non-signal events. Signals and non-signals were presented randomly and unpredictably. The task generated all four response types of a sustained attention task, i.e., hits, misses, correct rejections, false alarms. Infusions of the scrambled sequence ODNs did not affect performance. Likewise, infusions of the GAD67 ODNs failed to produce any effect. However, infusions of the GAD65 ODNs into the nucleus accumbens resulted in a robust and reliable decrease in the relative number of hits. Similarly, the combined infusion of GAD65+67 ODNs impaired the hit rate but did not affect the animals' ability to reject non-signals. Following each treatment series, performance rapidly returned to baseline, further indicating the specificity and reversibility of the effects of the infusions of the ODNs. While these data suggest that translation arrest of specifically the GAD65 isoform of the enzyme in the nucleus accumbens impairs attentional performance, the neuronal mechanisms mediating these effects remain unsettled.

摘要

在一项旨在评估持续注意力的任务中,测试了将针对谷氨酸脱羧酶(GAD65;GAD67)两种同工型的反义寡脱氧核苷酸(ODN)双侧注入伏隔核对完整大鼠行为表现的影响。该任务要求动物区分信号和非信号事件。信号和非信号随机且不可预测地呈现。该任务产生了持续注意力任务的所有四种反应类型,即击中、未击中、正确拒斥、误报。注入乱序序列ODN不影响行为表现。同样,注入GAD67 ODN也未产生任何影响。然而,将GAD65 ODN注入伏隔核导致击中的相对数量显著且可靠地减少。类似地,联合注入GAD65 + 67 ODN损害了命中率,但不影响动物拒斥非信号的能力。在每个治疗系列之后,行为表现迅速恢复到基线,进一步表明注入ODN的效果具有特异性和可逆性。虽然这些数据表明伏隔核中该酶的GAD65同工型的翻译停滞会损害注意力表现,但介导这些影响的神经机制仍未明确。

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