Cognitive impulsivity in animal models: Role of response time and reinforcing rate in delay intolerance with two-choice operant tasks

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• 作者：Walter Adriani ; Francesca Zoratto ; Emilia Romano ; Giovanni Laviola
• 关键词：ADHD ; Temporal discounting ; Serotonin 7 receptor ; Rat
• 刊名：Neuropharmacology
• 出版年：2010
• 出版时间：March-April 2010
• 年：2010
• 卷：58
• 期：4-5
• 页码：694-701
• 全文大小：378 K

文摘

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.