Inoue T, Izumi T, Maki Y, Muraki I, Koyama T
Department of Psychiatry, Hokkaido University School of Medicine, North 15, West 7, Kit a-ku, 060-8638, Sapporo, Japan.
Pharmacol Biochem Behav. 2000 Jul;66(3):573-8. doi: 10.1016/s0091-3057(00)00254-9.
The authors previously reported that typical and atypical antipsychotic drugs inhibited the acquisition but not expression of conditioned fear. The present study examined the effects of the selective dopamine D(1/5) agonist (SKF 38393) and antagonist (SCH 23390) on the acquisition and expression of conditioned fear. Drugs were administered subcutaneously to male Sprague-Dawley rats 30 min before foot shock (2.5 mA for 5 min). Twenty-four hours after foot shock, rats were again placed and observed in the shock chamber without shocks (conditioned fear). Freezing behavior induced by conditioned fear, an index of anxiety or fear, was recorded using a time-sampling procedure. SCH 23390 (0.1-1 mg/kg) inhibited the acquisition of conditioned freezing. The administration of SCH 23390 at a dose of 0.1 mg/kg 30 min after foot shock did not affect conditioned freezing. Taken together, it is concluded that D(1/5) antagonism inhibits the acquisition of conditioned fear. SKF 38393 (3-20 mg/kg) failed to change the acquisition of conditioned fear. SCH 23390 or SKF 38393 administered prior to testing did not reduce the expression of conditioned fear. These results suggest that D(1/5) receptors may play a role in the development of fear or anxiety.
作者先前报道，典型和非典型抗精神病药物抑制条件性恐惧的获得，但不影响其表达。本研究考察了选择性多巴胺D(1/5)激动剂（SKF 38393）和拮抗剂（SCH 23390）对条件性恐惧获得和表达的影响。在足部电击（2.5 mA，持续5分钟）前30分钟，将药物皮下注射给雄性Sprague-Dawley大鼠。足部电击24小时后，将大鼠再次放入电击箱中，但不给予电击（条件性恐惧），并进行观察。使用时间抽样程序记录由条件性恐惧诱发的僵住行为，这是焦虑或恐惧的一个指标。SCH 23390（0.1 - 1 mg/kg）抑制条件性僵住的获得。足部电击后30分钟给予0.1 mg/kg剂量的SCH 23390不影响条件性僵住。综合来看，得出结论：D(1/5)拮抗剂抑制条件性恐惧的获得。SKF 38393（3 - 20 mg/kg）未能改变条件性恐惧的获得。在测试前给予SCH 23390或SKF 38393不会降低条件性恐惧的表达。这些结果表明，D(1/5)受体可能在恐惧或焦虑的发展中起作用。
