Frederick D L, Allen J D
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079-9502, USA.
Pharmacol Biochem Behav. 1996 Apr;53(4):759-64. doi: 10.1016/0091-3057(95)02103-5.
Dopamine (DA) D1- and D2-agonists and antagonists were administered at fixed doses to assess putative dopaminergic involvement in timing behavior in rats performing under a peak-interval schedule. Significant shifts in response distributions to the left (consistent with the overestimation of the passage of time) were observed after treatment with the D1- and D2-agonists SKF 38393 and quinpirole, respectively. Both DA antagonists, eticlopride (D2) and SCH 23390 (D1), shifted the response distributions to the right (consistent with the underestimation of the passage of time), but neither drug produced statistically significant shifts. Based on percent shift in peak time from predrug baseline values, no significant differences were detected between agents as a function of their reported affinities for the D1- or D2-receptors. Results indicate the need for a systematic evaluation of each drug at various doses and a more detailed examination of the use of temporal schedules in predicting the efficacy of psychotherapeutic agents.
以固定剂量给予多巴胺(DA)D1和D2激动剂及拮抗剂,以评估假定的多巴胺能参与在峰值间隔时间表下执行任务的大鼠的定时行为。在用D1激动剂SKF 38393和D2激动剂喹吡罗治疗后,观察到反应分布分别向左显著移动(与时间流逝的高估一致)。两种DA拮抗剂,即依托必利(D2)和SCH 23390(D1),使反应分布向右移动(与时间流逝的低估一致),但两种药物均未产生统计学上的显著移动。根据从给药前基线值开始的峰值时间的百分比变化,未检测到各药物之间因其对D1或D2受体的报道亲和力而产生的显著差异。结果表明需要对每种药物在不同剂量下进行系统评估,并更详细地研究时间安排在预测心理治疗药物疗效方面的应用。