Witkin J M, Schindler C W, Tella S R, Goldberg S R
Preclinical Pharmacology Branch, NIDA Addiction Research Center, Baltimore, MD 21224.
Psychopharmacology (Berl). 1991;104(4):425-31. doi: 10.1007/BF02245644.
Involvement of D1 and D2 dopamine receptors in the effects of cocaine on schedule-controlled behavior was evaluated in squirrel monkeys responding under a multiple fixed-interval 5-min, fixed-ratio 10 schedule (mult FI FR) of food delivery. Cocaine and the D2 agonist quinpirole increased responding under the F1 at certain doses and disrupted the temporal patterning of behavior. Higher doses of these drugs decreased responding. In contrast, the D1 agonist SKF 38393 was devoid of behavioral activity up to 10 mg/kg where response suppression was obtained without significant modification of the temporal distribution of responding. The D2 antagonist haloperidol (0.001-0.03 mg/kg) did not alter the behavioral effects of cocaine up to doses that had pronounced behavioral effects on their own. However, haloperidol attenuated the behavioral effects of quinpirole. In contrast, the D1 antagonist SCH 23390 partially attenuated the response rate-suppressant effects of cocaine without blocking cocaine-induced disruptions of temporal response patterning. SCH 23390 did not antagonize the behavioral effects of SKF 38393. These results suggest that independent stimulation of either D1 or D2 receptors alone does not play a major role in the effects of cocaine on schedule-controlled behavior of squirrel monkeys.
在松鼠猴按多重固定间隔5分钟、固定比率10的食物投递时间表(多重FI FR)做出反应的过程中,评估了D1和D2多巴胺受体在可卡因对时间表控制行为的影响中的作用。可卡因和D2激动剂喹吡罗在某些剂量下增加了在固定间隔期间的反应,并扰乱了行为的时间模式。这些药物的更高剂量降低了反应。相比之下,D1激动剂SKF 38393在高达10mg/kg时没有行为活性,在该剂量下获得了反应抑制,而反应的时间分布没有显著改变。D2拮抗剂氟哌啶醇(0.001 - 0.03mg/kg)在达到自身具有显著行为效应的剂量时,并未改变可卡因的行为效应。然而,氟哌啶醇减弱了喹吡罗的行为效应。相比之下,D1拮抗剂SCH 23390部分减弱了可卡因的反应率抑制效应,但未阻断可卡因引起的时间反应模式破坏。SCH 23390并未拮抗SKF 38393的行为效应。这些结果表明,单独刺激D1或D2受体在可卡因对松鼠猴时间表控制行为的影响中并不起主要作用。