Cheung T H C, Bezzina G, Hampson C L, Body S, Fone K C F, Bradshaw C M, Szabadi E
Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Medical School, Queen's Medical Centre, Nottingham, UK.
Psychopharmacology (Berl). 2007 Aug;193(3):423-36. doi: 10.1007/s00213-007-0798-8. Epub 2007 May 6.
Operant timing behaviour is sensitive to dopaminergic manipulations. It has been proposed that this effect is mediated principally by D(2)-like dopamine receptors. However, we recently found that the effect of d-amphetamine on timing in the free-operant psychophysical procedure was mediated by D(1)-like dopamine receptors. It has not been established whether stimulation of D(2)-like receptors affects timing in this schedule.
To examine the effects of a D(2)-like receptor agonist quinpirole on second-range timing and the ability of dopamine receptor antagonists to reverse quinpirole's effects.
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 rates [percent responding on B (%B) vs time (t)] under each treatment; quantitative timing indices [T (50) (value of t when %B = 50) and Weber fraction] were compared among treatments.
Quinpirole (0.04, 0.08 mg kg(-1)) reduced T (50). This effect was attenuated by D(2)-like receptor antagonists haloperidol (0.05, 0.1 mg kg(-1)), eticlopride (0.04, 0.08 mg kg(-1)) and sulpiride (30, 60 mg kg(-1)), but not by the D(3) receptor-preferring antagonist nafadotride (0.5, 1 mg kg(-1)), the D(4) receptor antagonist L-745870 (1, 3 mg kg(-1)) or the D(1)-like receptor antagonist SKF-83566 (0.015 mg kg(-1)).
Results suggest that quinpirole reduced T (50) via an action at D(2) receptors. D(1)-like and D(2)-like receptors may mediate behaviourally similar but pharmacologically distinct effects on timing behaviour.
操作性定时行为对多巴胺能操作敏感。有人提出这种效应主要由D（2）样多巴胺受体介导。然而，我们最近发现右旋苯丙胺在自由操作心理物理学程序中对定时的影响是由D（1）样多巴胺受体介导的。尚未确定刺激D（2）样受体是否会影响此实验安排中的定时。
研究D（2）样受体激动剂喹吡罗对秒级定时的影响以及多巴胺受体拮抗剂逆转喹吡罗作用的能力。
大鼠在自由操作心理物理学实验安排下对两个杠杆（A和B）做出反应，在50秒的实验中，前半段对A杆的反应和后半段对B杆的反应会间歇性地得到强化。对每种处理下的相对反应率[对B杆的反应百分比（%B）与时间（t）]拟合逻辑函数；比较各处理之间的定量定时指标[T（50）（%B = 50时的t值）和韦伯分数]。
喹吡罗（0.04、0.08 mg kg⁻¹）降低了T（50）。D（2）样受体拮抗剂氟哌啶醇（0.05、0.1 mg kg⁻¹）、艾替必利（0.04、0.08 mg kg⁻¹）和舒必利（30、60 mg kg⁻¹）减弱了这种效应，但对D（3）受体选择性拮抗剂萘法朵利（0.5、
