Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys.
Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys.
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发表时间：
1989-10
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通讯作者：
J. Bergman;B. Madras;S. E. Johnson;R. Spealman
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作者：
J. Bergman;B. Madras;S. E. Johnson;R. Spealman
可卡因的自我给药与安非他酮、1-（2-[双（4-氟苯基）甲氧基]乙基]-4-（3-苯基丙基）哌嗪、马吲哚、哌甲酯和诺米芬辛的自我给药进行了比较，这些药物将[3 H]可卡因从其结合位点置换，并具有与可卡因相同的单胺摄取抑制作用。松鼠猴在随后静脉注射药物的二阶固定间隔时间表下作出反应，并通过确定生理盐水和各种药物剂量范围内维持的稳定反应率来建立剂量效应曲线。可卡因（0.01-0.56 mg/kg/注射），安非他酮（0.1-3.0 mg/kg/注射）、1-（2-[双（4-氟苯基）甲氧基]乙基）-4-（三氟甲基）苯甲酰胺（3-苯丙基）哌嗪-（0.03-1.0 mg/kg/注射），哌甲酯（0.01-0.3 mg/kg/注射）和诺米芬辛（0.01-0.3 mg/kg）在所有受试者中保持了相当的反应速率和模式，而马吲哚（0.03-0.3 mg/kg）仅在所研究的一半猴子中保持了自我给药行为。本研究结果与先前在松鼠猴中进行的研究结果相结合，揭示了可卡因和相关药物维持静脉自我给药和增加时间表控制反应速率的相对效力之间的密切对应关系，表明药物的强化和精神运动刺激作用是类似介导的。本研究中观察到的效力关系也与猴尾壳核中特异性结合的[3 H]可卡因的置换所观察到的效力关系基本一致，这表明可卡因的增强作用涉及其在脑中特定识别位点的作用。
The self-administration of cocaine was compared with that of bupropion, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine, mazindol, methylphenidate and nomifensine, drugs that displace [3H]cocaine from its binding sites and have monoamine uptake inhibiting effects in common with those of cocaine. Squirrel monkeys responded under a second-order fixed-interval schedule of consequent i.v. drug injection, and dose-effect curves were established by determining stable rates of responding maintained by saline and a range of doses of each drug. Cocaine (0.01-0.56 mg/kg/injection), bupropion (0.1-3.0 mg/kg/injection), 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3- phenylpropyl)piperazine-(0.03-1.0 mg/kg/injection), methylphenidate (0.01-0.3 mg/kg/injection) and nomifensine (0.01-0.3 mg/kg) maintained comparable rates and patterns of responding in all subjects, whereas mazindol (0.03-0.3 mg/kg) maintained self-administration behavior in only half the monkeys studied. The present results in conjunction with those of previous studies in squirrel monkeys reveal a close correspondence between the relative potencies of cocaine and related drugs for maintaining i.v. self-administration and for increasing rates of schedule-controlled responding, suggesting that the reinforcing and psychomotor-stimulant effects of the drugs are mediated similarly. The potency relations observed in the present study also agree generally with those observed for displacement of specifically bound [3H]cocaine in monkey caudate-putamen suggesting that the reinforcing effects of cocaine involve its actions at specific recognition sites in brain.