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精神药物对大鼠在涉及延迟强化物选择的操作性范式中反应的影响。

Effects of psychotropic drugs on rat responding in an operant paradigm involving choice between delayed reinforcers.

作者信息

Charrier D, Thiébot M H

机构信息

INSERM U-288, Faculty of Medicine Pitié-Salpêtrière, Paris, France.

出版信息

Pharmacol Biochem Behav. 1996 May;54(1):149-57. doi: 10.1016/0091-3057(95)02114-0.

Abstract

Preference for immediate reward, taken as an index of impulsiveness, has been suggested to be under the preferential control of central serotonin (5-HT) function. The present study examined the effects of the acute administration of drugs which directly or indirectly alter 5-HT transmission on tolerance to delay of reward in rats subjected to a procedure of discrete-trial choice in an operant chamber. Different groups of rats were trained to choose between two levers giving access to reinforcers differing in both magnitude and delay: one food pellet, delayed by 0 or 5 s, vs. five pellets delivered after a prereinforcer interval fixed at either 15, 30, 45, or 60 s, depending on the experiments. The learning curves indicated that rats were able to adjust their choice strategy precisely according to various factors: the respective duration of the delays before the small and large rewards, the immediacy of the small reward delivery, and the lengthening of the trials by a postreinforcer delay (or intertrial interval). Whatever the experimental parameters and stage of the learning, an acute administration of drugs able to reduce 5-HT neuronal activity (benzodiazepines; 5-HT1A receptor partial agonists: buspirone and MDL 73005EF) or enhance 5-HT transmission (5-HT reuptake inhibitors: indalpine and zimelidine; 5-HT1A receptor full agonist: 8-OH-DPAT) failed significantly to alter choice strategy (decreased or increased preference for the large but delayed reward, respectively), as they did in other situations such as a T-maze procedure. Only d-amphetamine (0.5 mg/kg), on one occasion, significantly reduced preference for the larger reward. The choice strategy was also insensitive to acute changes in experimental parameters such as a reduction in delay or increase in the magnitude of the large reinforcement. These results indicate that the present operant paradigm is not sensitive to acute modifications in the internal state of the animals and in the reward contingencies, and therefore is not useful to evaluate tolerance to delay and variations in impulsiveness in rats.

摘要

将即时奖励偏好作为冲动性指标,有人认为它受中枢5-羟色胺(5-HT)功能的优先控制。本研究考察了直接或间接改变5-HT传递的药物急性给药对大鼠奖励延迟耐受性的影响,这些大鼠在操作箱中接受离散试验选择程序。不同组的大鼠被训练在两个杠杆之间进行选择,这两个杠杆可获得大小和延迟不同的强化物:一粒食物颗粒,延迟0或5秒,与五粒食物颗粒在固定的前强化间隔15、30、45或60秒后给予,具体取决于实验。学习曲线表明,大鼠能够根据各种因素精确调整其选择策略:小奖励和大奖励之前延迟的各自持续时间、小奖励交付的即时性以及强化后延迟(或试验间隔)导致的试验延长。无论实验参数和学习阶段如何,能降低5-HT神经元活性的药物(苯二氮卓类;5-HT1A受体部分激动剂:丁螺环酮和MDL 73005EF)或增强5-HT传递的药物(5-HT再摄取抑制剂:茚氯嗪和齐美利定;5-HT1A受体完全激动剂:8-OH-DPAT)急性给药均未能显著改变选择策略(分别降低或增加对大但延迟奖励的偏好),就像在其他情况如T迷宫程序中那样。只有一次,右旋苯丙胺(0.5毫克/千克)显著降低了对较大奖励的偏好。选择策略对实验参数的急性变化也不敏感,如延迟减少或大强化量增加。这些结果表明,当前的操作范式对动物内部状态和奖励意外情况的急性改变不敏感,因此对于评估大鼠的奖励延迟耐受性和冲动性变化没有用处。

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