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, Room B109, Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
Psychopharmacology (Berl). 2007 Dec;195(2):213-22. doi: 10.1007/s00213-007-0892-y. Epub 2007 Aug 1.
Temporal differentiation of operant behaviour is sensitive to dopaminergic manipulations. Previous studies using the fixed-interval peak procedure implicated D(2)-like dopamine receptors in these effects. However, recent findings suggest that d-amphetamine alters timing performance on the free-operant psychophysical procedure via D(1)-like receptors. It is not known whether this effect of d-amphetamine is mimicked by direct D(1)-like receptor stimulation.
The effects of a D(1)-like receptor agonist 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine (SKF-81297) on performance on the free-operant psychophysical procedure and the interaction between SKF-81297 and a D(1)-like receptor antagonist 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SKF-83566) and a D(2)-like receptor antagonist haloperidol, were examined.
Rats were trained to respond on two levers (A and B) under a free-operant psychophysical schedule, in which sucrose reinforcement was provided intermittently for responding on A during the first half and on B during the second half of 50-s trials. Logistic psychometric functions were fitted to the relative response rate data (percent responding on B [%B] vs time from trial onset [t]) under each treatment condition, and quantitative indices of timing (T(50) [value of t corresponding to %B = 50] and the Weber fraction [(T(75)-T(25))/2T(50); T(25) and T(75) are values of t corresponding to %B = 25 and %B = 75] were compared among treatments.
SKF-81297 (0.8 mg kg(-1)) reduced T(50); this effect was antagonized by SKF-83566 (0.03 mg kg(-1)) but not by haloperidol (0.05, 0.1 mg kg(-1)).
Stimulation of D(1)-like dopamine receptors affects performance in the free-operant psychophysical procedure.
操作性行为的时间分化对多巴胺能操作敏感。以往使用固定间隔峰值程序的研究表明，D(2)样多巴胺受体参与了这些效应。然而，最近的研究结果表明，右旋苯丙胺通过D(1)样受体改变了自由操作心理物理学程序中的时间表现。目前尚不清楚右旋苯丙胺的这种效应是否能被直接的D(1)样受体刺激所模拟。
研究D(1)样受体激动剂6-氯-2,3,4,5-四氢-1-苯基-1H-3-苯并氮杂卓（SKF-81297）对自由操作心理物理学程序表现的影响，以及SKF-81297与D(1)样受体拮抗剂8-溴-2,3,4,5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂卓-7-醇（SKF-83566）和D(2)样受体拮抗剂氟哌啶醇之间的相互作用。
训练大鼠在自由操作心理物理学程序下对两个杠杆（A和B）做出反应，在50秒的试验中，前半段对A的反应和后半段对B的反应间歇性地给予蔗糖强化。将逻辑心理测量函数拟合到每种治疗条件下的相对反应率数据（B上的反应百分比[%B]与试验开始后的时间[t]），并比较各治疗组的时间定量指标（T(50) [对应%B = 50的t值]和韦伯分数[(T(75)-T(25))/2T(50)；T(25)和T(75)是对应%B = 25和%B = 75的t值]）。
SKF-81297（0.8 mg kg(-1)）降低了T(50)；这种效应被SKF-83566（0.03 mg kg(-1)）拮抗，但未被氟哌啶醇（0.05、0.1 mg kg(-1)）拮抗。
刺激D(1)样多巴胺受体影响自由操作心理物理学程序中的表现。
