Section of Behavioural Neuroscience, Department of Cell Biology & Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
Neuropharmacology. 2010 Mar-Apr;58(4-5):694-701. doi: 10.1016/j.neuropharm.2009.11.007. Epub 2009 Nov 27.
Impulsivity, a key symptom of ADHD (attention-deficit hyperactivity disorder), is also common in obsessive-compulsive and addictive disorders. There is rising interest in animal models of inhibitory-control impairment. Adolescent rats were tested daily in the intolerance-to-delay (ID) task (session 25 min, timeout 20 s), involving choice between either immediate small amount of food (SS), or larger amount of food after a delay (LL). The mixed 5-HT(1A/7) agonist (8-OH-DPAT, 0 or 0.060 mg/kg i.p.) was administered acutely just before the last three sessions at highest delays. In addition to the classical choice parameter (percent LL preference), the spontaneous waiting (termed response time, RT) occurring between end of a timeout (TO) and next nose-poke was calculated. The pace between consecutive reinforcer deliveries is given by the mean inter-trial interval (mITI, i.e. TO + RT). Hence, the impact of any given delay may be proportional to this pace and be expressed as delay-equivalent odds, i.e. the extent by which delays are multiples of the mITI. Data revealed that RT/mITI increased sharply from around 15 s/35 s to around 30 s/50 s when imposed delay changed from 30 s to 45 s (i.e. odds from 0.91 to 1.06). This suggests that rats adopted a strategy allowing them to keep in pace with perceived reinforcing rate. The increasing delay constraint directly influenced the length of rats' spontaneous waiting (RT) before next decision. For higher delays, with odds >1, rats shifted to a clear-cut SS preference, which is devoid of any exogenous temporal constraint. A challenge with 8-OH-DPAT (0 or 0.060 mg/kg i.p.) decreased impulsive choice but also increased RT. Thus, tapping onto 5-HT(1A/7) receptors slightly enhanced RT/mITI values, possibly reflecting ability of rats to cope with slower reinforcing rates and/or with delay-cancelled reward paces. In summary, delay-induced states of aversion may arise from the innate tendency to rely on a regular rate of reinforcement. Conversely, a drug-enhanced capacity to cope with delay may involve an internal ability to adjust expectancy about such a reinforcing rate.
冲动是注意力缺陷多动障碍（ADHD）的一个关键症状，在强迫症和成瘾障碍中也很常见。人们对抑制控制损伤的动物模型越来越感兴趣。青少年大鼠每天在不耐受延迟（ID）任务中接受测试（会议持续 25 分钟，超时 20 秒），涉及到立即选择少量食物（SS）或延迟后选择大量食物（LL）之间的选择。混合 5-HT（1A/7）激动剂（8-OH-DPAT，0 或 0.060mg/kg 腹腔注射）在最高延迟的最后三个会议前急性给药。除了经典的选择参数（LL 偏好百分比）外，还计算了在超时（TO）结束和下一次鼻刺之间发生的自发等待（称为反应时间，RT）。连续强化物传递之间的速度由平均试验间间隔（mITI，即 TO+RT）给出。因此，任何给定延迟的影响可能与该速度成正比，并表示为延迟等效几率，即延迟是 mITI 的倍数的程度。数据显示，当施加的延迟从 30 秒变为 45 秒时，RT/mITI 从大约 15 秒/35 秒急剧增加到大约 30 秒/50 秒（即几率从 0.91 变为 1.06）。这表明大鼠采用了一种策略，使它们能够与感知的强化率保持同步。不断增加的延迟约束直接影响大鼠在下一个决定前自发等待（RT）的时间长度。对于更高的延迟，几率大于 1，大鼠转变为明确的 SS 偏好，这种偏好没有任何外部时间约束。8-OH-DPAT（0 或 0.060mg/kg 腹腔注射）的挑战降低了冲动选择，但也增加了 RT。因此，稍微刺激 5-HT（1A/7）受体可提高 RT/mITI 值，可能反映了大鼠应对较慢强化率和/或延迟取消奖励速度的能力。总之，延迟引起的厌恶状态可能源于依赖于常规强化率的内在倾向。相反，药物增强应对延迟的能力可能涉及对这种强化率的期望进行内部调整的能力。
