Effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on performance on two operant timing schedules
Effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on performance on two operant timing schedules
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DOI：
10.1007/s002130000495
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发表时间：
2000-09-01
影响因子：
3.4
通讯作者：
Szabadi, E
中科院分区：
文献类型：
--
作者：
Chiang, TJ;Al-Ruwaitea, ASA;Szabadi, E
理论基础：以前的实验已经表明，中枢5-羟色胺耗竭对间期计时行为的破坏作用严重依赖于所使用的特定计时时间表。然而，目前尚不清楚作用于5-羟色胺受体的药物对5-羟色胺能功能的急性干扰是如何影响时间的。目的：观察5-羟色胺受体激动剂8-羟基-2-(二正丙氨基)四氢呋喃(8-OH-DPAT)对两种定量时序的影响。在两种时序中，自由操作时序训练大鼠在50次S试验(自由操作心理物理过程)和离散试验时程中训练大鼠辨别光刺激的持续时间(间隔等分任务)。方法：实验一：在50只S实验中，大鼠在自由操作的心理物理程序下进行A、B两个水平的反应训练，试验的前半部分对A、B两个水平的反应进行间歇性强化。对于一组，允许在杠杆之间重复切换；对于另一组，这是被阻止的。在实验2中，训练大鼠在2-S刺激后按下杠杆A，在8-S刺激后按下杠杆B，然后进行中等持续时间的刺激测试。其中一组在刺激呈现后需要“拨动反应”(按下中央托盘盖)来影响杠杆呈现；对于另一组，这一要求并不起作用。在这两个实验中，时间的定量指标都是从心理物理功能(反应与时间的反应%B)中得出的。结果：实验1中，8-羟基-DPAT(25、50、100、200 mU·kg~(-1)S.C.)在两个版本的时间表中，将心理物理曲线向左移动。在实验2中，8-OH-DPAT在不移动曲线的情况下增加了两个版本任务中的Weber分数。结论：这些结果表明8-OH-DPAT扰乱了时间行为。实验1的结果与5-羟色胺能机制有助于调节假想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。综上所述，这些结果支持不同的神经机制可能参与了计时任务，包括反应的时间分布和外部感觉刺激持续时间的辨别。
Rationale: 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. Objective: 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). Methods: 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). Results: In experiment 1, 8-OH-DPAT (25, 50, 100 and 200 mu g 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. Conclusions: 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.