Cheung T H C, Bezzina G, Asgari K, 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, Nottingham, NG7 2UH, UK.
Psychopharmacology (Berl). 2006 Apr;185(3):378-88. doi: 10.1007/s00213-006-0339-x. Epub 2006 Mar 15.
Temporal differentiation of operant behaviour is sensitive to dopaminergic manipulations. Studies using the fixed-interval peak procedure implicated D2 dopamine receptors in these effects. Less is known about the effects of dopaminergic manipulations on temporal differentiation in other timing schedules.
To examine the effects of a D1 antagonist,8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SKF-83566), and a D2 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.
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 [T50 (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.
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 T50; this effect was antagonised by SKF-83566 but not by haloperidol. Both antagonists reduced d-amphetamine-induced hyperlocomotion.
The results suggest that d-amphetamine's effect on performance in the free-operant psychophysical procedure is mediated by D1 rather than D2 receptors.
操作性行为的时间分辨对多巴胺能操作敏感。使用固定间隔峰值程序的研究表明D2多巴胺受体参与了这些效应。关于多巴胺能操作对其他计时程序中时间分辨的影响，人们了解较少。
研究D1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D2拮抗剂氟哌啶醇对自由操作心理物理学程序表现的影响，以及这些拮抗剂逆转儿茶酚胺释放剂d-苯丙胺对表现影响的能力。还研究了拮抗剂逆转d-苯丙胺诱导的运动亢进的能力。
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的反应会间歇性地得到强化。对每种治疗条件下的相对反应率数据（B上的反应百分比[%B]与时间[t]）拟合逻辑函数，并比较各治疗组之间的定量计时指标[T50（对应%B = 50时的t值）和韦伯分数]。在单独的实验中测量各治疗对运动的影响。
SKF-83566（0.015、0.03、0.06 mg kg⁻¹）不影响计时表现。氟哌啶醇（0.025、0.05 mg kg⁻¹）无影响；较高剂量（0.1 mg kg⁻¹）降低了T50。d-苯丙胺（0.4 mg kg⁻¹）降低了T50；这种效应被SKF-83566拮抗，但未被氟哌啶醇拮抗。两种拮抗剂都降低了d-苯丙胺诱导的运动亢进。
结果表明，d-苯丙胺对自由操作心理物理学程序表现的影响是由D1而非D2受体介导的。
