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酒精诱导的痕迹恐惧条件反射中的记忆损伤:一种海马体特异性效应。

Alcohol-induced memory impairment in trace fear conditioning: a hippocampus-specific effect.

作者信息

Weitemier Adam Z, Ryabinin Andrey E

机构信息

Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97201, USA.

出版信息

Hippocampus. 2003;13(3):305-15. doi: 10.1002/hipo.10063.

Abstract

It has been hypothesized that the amnesic effects of alcohol are through selective disruption of hippocampal function. Delay and trace fear conditioning are useful paradigms to investigate hippocampal-dependent and independent forms of memory. With delay fear conditioning, learning of explicit cues does not depend on normal hippocampal function, whereas learning explicit cues in trace fear conditioning does. In both delay and trace fear conditioning, the hippocampus is involved in learning to contextual cues, but it may not be entirely necessary. The present study investigates the effects of alcohol on the acquisition of delay and trace fear conditioning in mice, using freezing as a measure of learning. Male C57BL/6J mice were injected with 0.8 or 1.6 g/kg of 20% v/v alcohol and were immediately exposed to eight tone-footshock pairings in which the conditional stimulus (CS) either coterminated with a footshock unconditional stimulus (US) (delay conditioning) or was separated from the footshock by a 30-s trace interval (trace conditioning). During trace, but not delay fear conditioning, 0.8 g/kg alcohol impaired learning to a tone CS. This dose also impaired context-dependent learning in both procedures (although only slightly for trace fear conditioning). The 1.6 g/kg alcohol exerted a nonselective impairment on learning. The impairment by alcohol of learning to a tone CS when it is hippocampus-dependent, but not when it is hippocampus-independent provides further support for the hypothesis that alcohol exerts a selective effect on hippocampus-dependent learning.

摘要

有人提出假说认为,酒精的失忆作用是通过对海马体功能的选择性破坏来实现的。延迟和痕迹恐惧条件反射是研究海马体依赖性和非依赖性记忆形式的有用范式。在延迟恐惧条件反射中,对明确线索的学习不依赖于正常的海马体功能,而在痕迹恐惧条件反射中对明确线索的学习则依赖于正常的海马体功能。在延迟和痕迹恐惧条件反射中,海马体都参与对情境线索的学习,但可能并非完全必要。本研究使用僵住作为学习的衡量指标,探究了酒精对小鼠延迟和痕迹恐惧条件反射习得的影响。给雄性C57BL/6J小鼠注射0.8或1.6 g/kg的20% v/v酒精,然后立即让它们接受八次音调-足部电击配对,其中条件刺激(CS)要么与足部电击无条件刺激(US)同时结束(延迟条件反射),要么与足部电击之间有30秒的痕迹间隔(痕迹条件反射)。在痕迹恐惧条件反射而非延迟恐惧条件反射中,0.8 g/kg的酒精损害了对音调CS的学习。这个剂量在两种程序中也损害了情境依赖性学习(尽管对痕迹恐惧条件反射的损害较小)。1.6 g/kg的酒精对学习产生了非选择性损害。当对音调CS的学习依赖于海马体时酒精会损害学习,但当学习不依赖于海马体时则不会,这进一步支持了酒精对海马体依赖性学习有选择性作用的假说。

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