Effects of cocaine and related drugs in nonhuman primates. II. Stimulant effects on schedule-controlled behavior.
Effects of cocaine and related drugs in nonhuman primates. II. Stimulant effects on schedule-controlled behavior.
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发表时间：
1989-10
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通讯作者：
R. Spealman;B. Madras;J. Bergman
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作者：
R. Spealman;B. Madras;J. Bergman
可卡因的行为效应进行了比较，与几种可卡因衍生物和结构不同的药物，抑制单胺摄取。在可卡因同系物中，（-）-可卡因、（+）-假可卡因和1 α H，3 α，5 α H-托品烷-3-基-3，5-二氯苯甲酸酯产生剂量相关的应答率增加，而（-）-假可卡因、（+）-假可卡因和1 α H，3 α，5 α H-托品烷-3-基-3，5-二氯苯甲酸酯产生剂量相关的应答率增加。（-）-苯甲酰芽子碱和（-）-苯甲酰去甲芽子碱在100倍或更大剂量范围内没有一致地增加反应。选择性抑制多巴胺摄取的1-（2-[双（4-氟苯基）甲氧基]乙基）-4-（3-苯丙基）哌嗪，以及抑制多巴胺和其他单胺摄取的马吲哚、哌甲酯、诺米芬辛和安非他酮，具有与可卡因相似的行为效应。相反，地昔帕明和西酞普兰，选择性地抑制去甲肾上腺素和血清素的摄取，分别，只产生剂量相关的反应率下降。结合以前的研究结果表明，15种不同药物的效力之间的密切对应关系，产生可卡因样的行为效应，并取代特定结合的[3 H]可卡因在尾壳核。这些发现与可卡因和相关药物的行为效应与其在与多巴胺摄取系统相关的特定可卡因识别位点的作用有关的观点一致。
The behavioral effects of cocaine were compared with those of several cocaine derivatives and structurally distinct drugs that inhibit monoamine uptake. Squirrel monkeys were trained to respond under a fixed-interval schedule of stimulus-shock termination, and dose-effect curves were determined by administering cumulative doses i.v. Among the cocaine congeners, (-)-cocaine, (+)-pseudococaine and 1 alpha H, 3 alpha, 5 alpha H-tropan-3-yl-3,5-dichlorobenzoate produced dose-related increases in response rate, whereas (-)-pseudococaine, (-)-benzoylecgonine and (-)-benzoylnorecgonine did not increase responding consistently over a 100-fold or greater range of doses. 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine, which selectively inhibits uptake of dopamine, and mazindol, methylphenidate, nomifensine and bupropion, which inhibit uptake of dopamine as well as other monoamines, had behavioral effects similar to those of cocaine. In contrast, desipramine and citalopram, which selectively inhibit uptake of norepinephrine and serotonin, respectively, produced only dose-related decreases in response rate. The results combined with previous studies demonstrate a close correspondence between the potencies of 15 different drugs for producing cocaine-like behavioral effects and for displacing specifically bound [3H]cocaine in caudate-putamen. These findings are consistent with the view that the behavioral effects of cocaine and related drugs are linked to their actions at specific cocaine recognition sites associated with the dopamine uptake system.