Evidence for a role of D1 dopamine receptors in d-amphetamine's effect on timing behaviour in the free-operant psychophysical procedure
Evidence for a role of D1 dopamine receptors in d-amphetamine's effect on timing behaviour in the free-operant psychophysical procedure
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DOI：
10.1007/s00213-006-0339-x
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发表时间：
2006-04-01
影响因子：
3.4
通讯作者：
Szabadi, E
中科院分区：
文献类型：
--
作者：
Cheung, THC;Bezzina, G;Szabadi, E
理由：操作行为的时间分化对多巴胺能操作敏感。使用固定间隔峰值程序的研究表明 D-2 多巴胺受体与这些效应有关。关于多巴胺能操作对其他时间安排中时间分化的影响知之甚少。目的：检查 D-1 拮抗剂 8-溴-2,3,4,5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂平-7-ol (SKF-83566) 和 D-2 拮抗剂氟哌啶醇对自由操作心理物理程序的影响，以及这些拮抗剂逆转儿茶酚胺释放剂 d-苯丙胺对性能。还检查了拮抗剂逆转 d-苯丙胺诱导的过度运动的能力。材料和方法：在自由操作的心理物理计划下，大鼠对两个杠杆（A 和 B）做出反应，在 50 秒的试验中，前半部分对 A 做出反应，后半部分对 B 做出反应，间歇性地提供强化。将逻辑函数拟合到每种治疗条件下的相对响应率数据（B 响应百分比 [%B] vs 时间 [t]），并在治疗之间比较定量计时指数 [T (50)（t 值对应于 %B=50）和韦伯分数]。在单独的实验中测量了治疗对运动的影响。结果：SKF-83566（0.015、0.03、0.06 mg kg(-1)）不影响计时性能。氟哌啶醇（0.025、0.05mg·kg(-1)）无作用；较高剂量(0.1 mg kg(-1))降低了T (50)。 d-安非他明（0.4 mg kg(-1)）降低T（50）；该效应可被 SKF-83566 拮抗，但不能被氟哌啶醇拮抗。两种拮抗剂都能减少 d-苯丙胺引起的过度运动。结论：结果表明，d-苯丙胺对自由操作心理物理程序中表现的影响是由 D-1 受体介导的，而不是 D-2 受体介导的。
Rationale: Temporal differentiation of operant behaviour is sensitive to dopaminergic manipulations. Studies using the fixed-interval peak procedure implicated D-2 dopamine receptors in these effects. Less is known about the effects of dopaminergic manipulations on temporal differentiation in other timing schedules. Objective: To examine the effects of a D-1 antagonist,8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SKF-83566), and a D-2 antagonist, haloperidol, on performance on the free-operant psychophysical procedure, and the ability of these antagonists to reverse the effects of the catecholamine-releasing agent, d-amphetamine on performance. The antagonists' ability to reverse d-amphetamine-induced hyperlocomotion was also examined. Materials and methods: Rats responded on two levers (A and B) under a free-operant psychophysical schedule, in which reinforcement was provided intermittently for responding on A during the first half, and B during the second half, of 50-s trials. Logistic functions were fitted to the relative response rate data (percent responding on B [%B] vs time [t]) in each treatment condition, and quantitative timing indices [T (50) (value of t corresponding to %B=50) and Weber fraction] were compared among treatments. Effects of the treatments on locomotion were measured in a separate experiment. Results: SKF-83566 (0.015, 0.03, 0.06 mg kg(-1)) did not affect timing performance. Haloperidol (0.025, 0.05 mg kg(-1)) had no effect; a higher dose (0.1 mg kg(-1)) reduced T (50). d-Amphetamine (0.4 mg kg(-1)) reduced T (50); this effect was antagonised by SKF-83566 but not by haloperidol. Both antagonists reduced d-amphetamine-induced hyperlocomotion. Conclusions: The results suggest that d-amphetamine's effect on performance in the free-operant psychophysical procedure is mediated by D-1 rather than D-2 receptors.