Chiang T J, Al-Ruwaitea A S, Mobini S, Ho M Y, Bradshaw C M, Szabadi E
Division of Psychiatry, University of Nottingham, Medical School, Queen's Medical Centre, UK.
Psychopharmacology (Berl). 2000 Sep;151(4):379-91. doi: 10.1007/s002130000495.
Previous experiments have shown that the disruptive effect of central 5-HT depletion on interval timing behaviour is critically dependent upon the particular timing schedule used. However, it is not known how acute disruption of 5-HTergic function brought about by drugs acting at 5-HT receptors affects timing.
To examine the effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on performance on two quantitative timing schedules, a free-operant schedule in which rats were trained to distribute their responses differentially between two levers during the course of a 50-s trial (free-operant psychophysical procedure) and a discrete-trials schedule in which rats were trained to discriminate the durations of light stimuli (interval bisection task).
In experiment 1, rats were trained under the free-operant psychophysical procedure to respond on two levers (A and B) in 50-s trials in which reinforcement was provided intermittently for responding on A in the first half, and B in the second half, of the trial. For one group, repetitive switching between levers was permitted; for another group, it was prevented. In experiment 2, rats were trained to press lever A after a 2-s stimulus and lever B after an 8-s stimulus, and were then tested with stimuli of intermediate durations. For one group, a 'poke response' (depression of a central tray flap) was required after stimulus presentation to effect lever presentation; for the other group this requirement did not operate. In both experiments, quantitative indices of timing were derived from the psychophysical functions (%B responding vs time).
In experiment 1, 8-OH-DPAT (25, 50, 100 and 200 microg kg(-1) s.c.) displaced the psychophysical curve to the left in both versions of the schedule. In experiment 2, 8-OH-DPAT increased the Weber fraction in both versions of the task without displacing the curve.
These results show that 8-OH-DPAT disrupts timing behaviour. The results of experiment 1 are consistent with the proposal that 5-HTergic mechanisms help to regulate the period of the hypothetical pacemaker. However, the results of experiment 2 do not support this suggestion. Taken together, the results support the notion that different neural mechanisms may be involved in timing tasks involving temporal distribution of responding and discrimination of the durations of exteroceptive stimuli.
先前的实验表明，中枢5-羟色胺（5-HT）耗竭对间隔计时行为的干扰作用严重依赖于所使用的特定计时方案。然而，尚不清楚作用于5-HT受体的药物所引起的5-HT能功能的急性破坏如何影响计时。
研究5-HT1A受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）对两种定量计时方案表现的影响，一种是自由操作方案，即训练大鼠在50秒的试验过程中在两个杠杆之间以不同方式分配反应（自由操作心理物理学程序）；另一种是离散试验方案，即训练大鼠辨别光刺激的持续时间（间隔二等分任务）。
在实验1中，大鼠按照自由操作心理物理学程序进行训练，在50秒的试验中对两个杠杆（A和B）做出反应，在试验的前半段对A杠杆的反应和后半段对B杠杆的反应会间歇性地给予强化。对于一组，允许在杠杆之间重复切换；对于另一组，则加以阻止。在实验2中，训练大鼠在2秒刺激后按压A杠杆，在8秒刺激后按压B杠杆，然后用中间持续时间的刺激进行测试。对于一组，在刺激呈现后需要一个“戳击反应”（按下中央托盘挡板）才能呈现杠杆；对于另一组则没有此要求。在两个实验中，计时的定量指标均来自心理物理学函数（%对B的反应与时间的关系）。
在实验1中，8-OH-DPAT（25、50、100和200微克/千克，皮下注射）在两种方案中均使心理物理学曲线向左移动。在实验2中，8-OH-DPAT在两种任务形式中均增加了韦伯分数，而没有使曲线移位。
这些结果表明8-OH-DPAT会干扰计时行为。实验1的结果与5-HT能机制有助于调节假设的起搏器周期的观点一致。然而，实验2的结果并不支持这一观点。综合来看，这些结果支持这样一种观点，即不同的神经机制可能参与涉及反应时间分布和外部感受刺激持续时间辨别的计时任务。
