Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms
Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms
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DOI：
10.1007/s002130050410
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发表时间：
1997-10-01
影响因子：
3.4
通讯作者：
Robbins, TW
中科院分区：
文献类型：
--
作者：
Harrison, AA;Everitt, BJ;Robbins, TW
一系列十个实验检查了中枢 5-HT 严重耗竭对五选择系列反应时间任务中大鼠注意力表现的影响，并确定了这种耗竭对 d-苯丙胺和选择性多巴胺受体拮抗剂影响的反应的影响。训练老鼠检测和定位随机出现在五个空间位置之一的短暂视觉刺激。当表现稳定时（> 80% 正确，< 20% 遗漏），在用去甲肾上腺素能和多巴胺能再摄取抑制剂预处理后，通过脑室内注射神经毒素 5,7-二羟色胺 (5,7-DHT) 诱导选择性中枢 5-HT 耗竭。受损动物执行五项选择的连续反应时间任务，其准确度与假手术对照组相同。然而，5-HT 消耗减少了省略试验的百分比，并增加了过早/预期反应的数量。 5-HT 消耗后的这种行为模式不能归因于主要动机的增强，如食物摄入量和收集食物强化潜伏期的测量所证明的那样。该损伤减弱了高剂量全身注射 d-苯丙胺引起的过早反应的增加。 5-HT 消耗也减弱了 (-)-舒必利（一种 D-2 受体拮抗剂）引起的剂量依赖性准确性下降，尽管该药物对两组反应延迟和过早反应的影响相似。然而，D-1 受体拮抗剂 SCH 23390 的全身给药阻断了病变产生的冲动反应，这表明病变对遗漏试验和过早反应的百分比缺乏影响。结果表明，中枢 5-HT 耗竭会导致冲动、快速反应，但这不会损害视觉辨别能力的准确性。冲动性的增加可能是通过改变 5-HT-多巴胺相互作用来介导的，病变消除了对多巴胺神经传递的抑制影响。
A series of ten experiments examined the effects of profound central 5-HT depletion on attentional performance in the rat in the five-choice serial reaction time task, and also determined the effects of such depletion on responding affected by d-amphetamine and by selective dopamine receptor antagonists. Rats were trained to detect and locate brief visual stimuli randomly presented in one of five spatial locations. When performance had stabilised (> 80% correct, < 20% omissions), selective central 5-HT depletion was induced by intracerebroventricular administration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) following pretreatment with both a noradrenergic and a dopaminergic re-uptake inhibitor. The lesioned animals performed the five-choice serial reaction time task with the same degree of accuracy as the sham-operated controls. However, 5-HT depletion reduced the percentage of omitted trials and increased the number of premature/anticipatory responses. This pattern of behaviour following 5-HT depletion could not be attributed to enhanced primary motivation as demonstrated by measures of food intake and latencies to collect food reinforcement. The lesion attenuated the increase of premature responding induced by high doses of systemically administered d-amphetamine. 5-HT depletion also attenuated the dose-dependent decrease in accuracy induced by (-)-sulpiride, a D-2 receptor antagonist, although the effects of this drug on response latencies and premature responding were similar in both groups. However, the systemic administration of the D-1 receptor antagonist, SCH 23390, blocked the impulsive responding produced by the lesion as indicated by a lack of lesion effects on the percentage of omitted trials and premature responding. The results suggest that central 5-HT depletion results in impulsive, fast responding, which nevertheless does not impair accuracy of visual discrimination performance. The increased impulsivity may be mediated by altered 5-HT-dopamine interactions, with the lesion removing an inhibitory influence over dopamine neurotransmission.