Evenden J L, Ryan C N
Preclinical Research and Development, Astra Arcus, S-151 85 Södertälje, Sweden.
Psychopharmacology (Berl). 1999 Oct;146(4):413-21. doi: 10.1007/pl00005486.
Tolerance to delay of reinforcement has been proposed as an important facet of self-control in both animals and man. Poor self-control, leading to impulsive behaviour, can be a major problem if it reaches pathological levels.
The effects of five serotonergic drugs were compared to those of ethanol on a procedure for measuring tolerance to delay of reinforcement in rats in order to elucidate further the role of the serotonin systems in the regulation of impulsive behaviour.
Rats were trained to choose between a single food pellet (small reinforcer) delivered immediately or five food pellets (large reinforcer) delivered after programmed delays. At the start of each session, there was no delay between the response and delivery of the large reinforcer, but this was increased stepwise during the session to delays of 10, 20, 40 and 60 s.
The rats showed consistent preference for the larger reinforcer when it was not delayed but showed a shift in preference as the session continued, so that they preferred the small reinforcer when the large was delayed by 40 or 60 s. Ethanol at a dose of 1.0 g/kg produced a significance increase in preference for the small, immediate reinforcer throughout the session, although there were marked individual differences in the size of the effect. A similar, but somewhat smaller effect was seen with the 5-HT(2) agonist, DOI, at a dose of 1.0 mg/kg. In contrast, the 5-HT(1A) agonist, 8-OH-DPAT (0.3 mg/kg) reduced preference for the large reinforcer at the start of the session, and reduced preference for the small reinforcer at the end of the session, i.e. produced a regression to indifference. Lower doses of these three drugs, and treatment with the 5-HT receptor subtype selective antagonists WAY-100635 (5-HT(1A): 0.01-0.1 mg/kg), ritanserin (5-HT(2): 0.1 and 0.3 mg/kg) and MDL-72222 (5-HT(3): 1.0 and 3.0 mg/kg) had no significant effects on reinforcer choice.
These data show that ethanol and DOI increase preference for the immediate reinforcer, which can be construed as evidence of an increase in impulsive behaviour (reduction in self control), whereas selective blockade of the 5-HT(1A), 5-HT(2) or 5-HT(3) receptors using selective antagonists does not affect self-control.
对强化延迟的耐受性已被认为是动物和人类自我控制的一个重要方面。如果自我控制能力差导致冲动行为达到病理水平,可能会成为一个主要问题。
比较五种血清素能药物与乙醇对大鼠强化延迟耐受性测量程序的影响,以进一步阐明血清素系统在调节冲动行为中的作用。
训练大鼠在立即给予的单个食物颗粒(小强化物)和经过设定延迟后给予的五个食物颗粒(大强化物)之间进行选择。在每个实验开始时,对大强化物的反应和给予之间没有延迟,但在实验过程中逐步增加到10、20、40和60秒的延迟。
当大强化物不延迟时,大鼠对其表现出一致的偏好,但随着实验的进行,偏好发生了转变,以至于当大强化物延迟40或60秒时,它们更喜欢小强化物。剂量为1.0克/千克的乙醇在整个实验过程中显著增加了对小的、即时强化物的偏好,尽管效果大小存在明显的个体差异。剂量为1.0毫克/千克的5-HT(2)激动剂DOI也有类似但稍小的效果。相比之下,5-HT(1A)激动剂8-OH-DPAT(0.3毫克/千克)在实验开始时降低了对大强化物的偏好,在实验结束时降低了对小强化物的偏好,即产生了向无差异的回归。这三种药物的较低剂量,以及用5-HT受体亚型选择性拮抗剂WAY-100635(5-HT(1A):0.01 - 0.1毫克/千克)、利坦色林(5-HT(2):0.1和0.3毫克/千克)和MDL-72222(5-HT(3):1.0和3.0毫克/千克)进行治疗,对强化物选择没有显著影响。
这些数据表明,乙醇和DOI增加了对即时强化物的偏好,这可以被解释为冲动行为增加(自我控制能力下降)的证据,而使用选择性拮抗剂对5-HT(1A)、5-HT(2)或5-HT(3)受体的选择性阻断不会影响自我控制。