Koskinen T, Ruotsalainen S, Puumala T, Lappalainen R, Koivisto E, Männistö P T, Sirviö J
A.I. Virtanen Institute, University of Kuopio, and University Hospital, Finland.
Neuropharmacology. 2000 Jan 28;39(3):471-81. doi: 10.1016/s0028-3908(99)00159-8.
The present experiments investigated the effects of agents acting at serotonin (5-HT)-2 receptors on the performance of rats in a choice serial reaction time (5-CSRT) task in order to examine the role of 5-HT2 receptors in the modulation of attention and response control. The results indicate that DOI, [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride; 0.05, 0.1 and 0.2 mg/kg, subcutaneously], a 5-HT(2A/2C) agonist, slightly impaired the choice accuracy of the well performing rats and markedly increased their premature responding. DOI (0.05 and 0.1 mg/kg) had no effect on the latency to collect earned food pellets or to respond correctly, indicating that these lower doses of DOI did not reduce motivation for the food reward in this task. The selective effect of a low dose of DOI (0.1 mg/kg) on premature responding was completely blocked by ketanserin (0.2 mg/kg), a 5-HT2A antagonist, and ritanserin (0.3 mg/kg), a 5-HT(2A/2C) antagonist, but only partially blocked by a high dose of SER082 (1.0 mg/kg), a 5-HT2C antagonist. In contrast to DOI, mCPP, [1-(3-phenyl)piperazine; 0.05 and 0.15 mg/kg], a 5-HT2C agonist, had no effect on choice accuracy or premature responding, but it reduced behavioral activity and/or arousal as indicated by the decreased number of trials completed and increased the probability of omissions. SER082 (1.0 mg/kg) blocked the effects of mCPP on performance. These data suggest that the overactivation of 5-HT2A receptors impairs response control in a 5-CSRT task, whereas the overactivation of 5-HT2C receptors can affect behavioral activity and/or arousal state of the animals for this food rewarded task.
本实验研究了作用于5-羟色胺（5-HT）-2受体的药物对大鼠在选择连续反应时（5-CSRT）任务中的行为表现的影响，以检验5-HT2受体在调节注意力和反应控制中的作用。结果表明，5-HT(2A/2C)激动剂DOI，即[(±)-1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷盐酸盐；0.05、0.1和0.2mg/kg，皮下注射]，略微损害了表现良好的大鼠的选择准确性，并显著增加了它们的过早反应。DOI（0.05和0.1mg/kg）对获取奖励食物颗粒或正确反应的潜伏期没有影响，表明这些较低剂量的DOI并没有降低该任务中对食物奖励的动机。低剂量的DOI（0.1mg/kg）对过早反应的选择性作用被5-HT2A拮抗剂酮色林（0.2mg/kg）和5-HT(2A/2C)拮抗剂利坦色林（0.3mg/kg）完全阻断，但仅被高剂量的5-HT2C拮抗剂SER082（1.0mg/kg）部分阻断。与DOI相反，5-HT2C激动剂mCPP，即[1-(3-苯基)哌嗪；0.05和0.15mg/kg]，对选择准确性或过早反应没有影响，但它降低了行为活动和/或觉醒，表现为完成的试验次数减少，并增加了遗漏的概率。SER082（1.0mg/kg）阻断了mCPP对行为表现的影响。这些数据表明，5-HT2A受体的过度激活会损害5-CSRT任务中的反应控制，而5-HT2C受体的过度激活会影响动物在这个食物奖励任务中的行为活动和/或觉醒状态。
