Wilkinson L S, Humby T, Killcross S, Robbins T W, Everitt B J
Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
Eur J Neurosci. 1996 Jul;8(7):1479-87. doi: 10.1111/j.1460-9568.1996.tb01610.x.
The experiments examined the release of 5-hydroxytryptamine using in vivo microdialysis methods in the hippocampus of freely moving rats following Pavlovian aversive conditioning to discrete and contextual stimuli. Differential conditioning was achieved by manipulating the interval between the offset of a discrete auditory 'clicker' stimulus and the onset of a mild foot-shock reinforcer (0.5 mA, 0.5 s). Foot-shock occurred either simultaneously with the last second of the discrete auditory stimulus (in short-trace subjects) or 60 s later (long-trace subjects). In this way, subjects were preferentially conditioned to the discrete stimulus and background 'contextual' stimuli respectively. During conditioning subjects also received two identical unpaired visual stimuli. At test, dialysates were collected and behavioural measures taken as all animals experienced (i) the aversive and two other 'neutral' environments, and (ii) the discrete unconditioned and conditioned stimuli presented in both aversive and neutral environments. Exposure to the aversive environment, but not to either of the two neutral environments, was associated with significantly increased hippocampal 5-hydroxytryptamine release in long-trace subjects. There was also a small but non-significant increase in 5-hydroxytryptamine release in short-trace animals. In contrast, hippocampal 5-hydroxytryptamine release was unaffected by presentation of either of the discrete stimuli under all conditions. The last result was obtained despite robust behavioural responses (freezing) to the discrete conditioned stimulus. These data do not agree with the hypothesis that aversive cues generally activate 5-hydroxytryptamine function in the hippocampus. Rather, they suggest a degree of specificity whereby 5-hydroxytryptamine release in the hippocampus was determined primarily by other qualitative properties of the conditioned aversive stimulus, namely whether the aversive cue was discrete or contextual, as well as by the magnitude of conditioning.
实验采用体内微透析方法，在自由活动大鼠的海马体中检测5-羟色胺的释放情况，这些大鼠经过巴甫洛夫式厌恶条件反射，对离散刺激和情境刺激产生反应。通过控制离散听觉“咔哒”声刺激的结束与轻微足部电击强化刺激（0.5毫安，0.5秒）开始之间的间隔来实现差异条件反射。足部电击要么与离散听觉刺激的最后一秒同时发生（短痕迹组），要么在60秒后发生（长痕迹组）。通过这种方式，实验对象分别优先对离散刺激和背景“情境”刺激形成条件反射。在条件反射过程中，实验对象还会接受两个相同的非配对视觉刺激。在测试时，收集透析液并进行行为测量，因为所有动物都经历了（i）厌恶环境和另外两个“中性”环境，以及（ii）在厌恶环境和中性环境中呈现的离散无条件刺激和条件刺激。暴露于厌恶环境中，而非两个中性环境中的任何一个，会使长痕迹组大鼠海马体中5-羟色胺的释放显著增加。短痕迹组动物的5-羟色胺释放也有小幅但不显著的增加。相比之下，在所有条件下，离散刺激的呈现均未影响海马体中5-羟色胺的释放。尽管对离散条件刺激有强烈的行为反应（僵住），但仍得到了最后的这个结果。这些数据与厌恶线索通常会激活海马体中5-羟色胺功能的假设不一致。相反，它们表明存在一定程度的特异性，即海马体中5-羟色胺的释放主要由条件性厌恶刺激的其他定性特征决定，即厌恶线索是离散的还是情境性的，以及条件反射的强度。
