Dopamine D-1 antagonist SCH23390 attenuates self-administration of both cocaine and fentanyl in rats
Dopamine D-1 antagonist SCH23390 attenuates self-administration of both cocaine and fentanyl in rats
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DOI：
10.1016/s1382-6689(97)00147-6
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发表时间：
1997-06-06
影响因子：
4.3
通讯作者：
Sato, S
中科院分区：
文献类型：
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作者：
Awasaki, Y;Nishida, N;Sato, S
为了研究多巴胺D-1受体在可卡因和芬太尼的强化作用中的作用，使用渐进比例（PR）强化方案在大鼠中研究了D-1拮抗剂SCH 23390对这些药物的静脉内自我给药的作用，在此期间，大鼠根据FR 1方案接受前三次注射。然后，在每三次进一步喷射之后，输送喷射所需的杠杆按压次数（杠杆按压比）增加三次。将每只大鼠在每6小时期间完成的最后一次杠杆按压比率指定为断裂点。在可卡因（每次注射0.125-1.00 mg/kg）和芬太尼（每次注射0.25-2.00 μ g/kg）自我给药期间，断裂点值呈剂量依赖性增加。用SCH 23390（0.01 mg/kg，s.c.）可卡因和芬太尼的断裂点值均降低，反映了药物增强效力的降低。为了确定SCH 23390的作用是否是由于杠杆按压反应的一般抑制，将SCH 23390（0.01 mg/kg，s.c.）对通过水强化维持的大鼠的性能的影响。SCH 23390仅短暂抑制性能，因此一般抑制似乎对断裂点影响很小或没有影响。这些结果表明，多巴胺D-1受体参与介导的精神兴奋剂可卡因和阿片类芬太尼的增强效果。(C)1997年Elsevier Science B.V.
To investigate the role of dopamine D-1 receptors in the reinforcing effects of cocaine and fentanyl, the effect of the D-1 antagonist SCH23390 on intravenous self-administration of these drugs was investigated in rats using a progressive ratio (PR) reinforcement schedule, during which the rats received the first three injections under an FR1 schedule. Then the number of lever presses required to deliver an injection (lever press ratio) increased by three after every three further injections. The last lever press ratio completed by each rat during each 6 h session was designated the breaking point. Breaking point values increased dose-dependently during both cocaine (0.125-1.00 mg/kg per injection) and fentanyl (0.25-2.00 mu g/kg per injection) self-administration. Pretreatment with SCH23390 (0.01 mg/kg, s.c.) decreased breaking point values for both cocaine and fentanyl, reflecting a decrease in the reinforcing efficacy of the drugs. To determine whether the effect of SCH23390 was due to general suppression of the lever pressing response, the effect of SCH23390 (0.01 mg/kg, s.c.) on the performance of rats maintained by water-reinforcement was examined. SCH23390 suppressed performance only transiently, therefore general suppression appears to have little or no effect on the breaking point. These results suggest that dopamine D-1 receptors are involved in mediating the reinforcing effects of both the psychostimulant cocaine and the opiate fentanyl. (C) 1997 Elsevier Science B.V.