Effects of monoamine releasers with varying selectivity for releasing dopamine/norepinephrine versus serotonin on choice between cocaine and food in rhesus monkeys.
Effects of monoamine releasers with varying selectivity for releasing dopamine/norepinephrine versus serotonin on choice between cocaine and food in rhesus monkeys.
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DOI：
10.1097/fbp.0b013e32834d63ac
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发表时间：
2011-12
影响因子：
1.6
通讯作者：
Negus SS
中科院分区：
文献类型：
--
作者：
Banks ML;Blough BE;Negus SS
单胺释放剂构成一类用于治疗可卡因滥用的候选药物，并且同时可卡因与食物选择程序作为评价候选药物的功效和安全性的实验工具是潜在有价值的。本研究评估了恒河猴在用5种单胺释放剂治疗期间对可卡因和食物的选择，所述单胺释放剂在促进多巴胺和去甲肾上腺素（DA/NE）与5-羟色胺（5 HT）释放的选择性方面不同[间氟苯丙胺、（+）-苯甲曲嗪、（+）-甲基苯丙胺、萘异丙胺和（±）-芬氟拉明]。恒河猴（n=8）在食物递送（1 g颗粒，固定比例100方案）和可卡因注射（0 - 0.1 mg/kg/inj，固定比例10方案）的同时选择方案下有反应。在用盐水或每种测试化合物剂量连续7天治疗期间，每天确定剂量选择剂量-效应曲线。在生理盐水处理期间，可卡因保持了可卡因选择的剂量依赖性增加，并且最高可卡因剂量（0.032 - 0.1 mg/kg/inj）保持了几乎完全的可卡因选择。单胺释放剂减少可卡因选择的功效对应于其释放DA/NE与5 HT的药理学选择性。没有释放减少可卡因的选择或促进响应食物选择的重新分配到相同程度的替代可卡因的盐水。这些结果扩展了DA/NE选择性释放剂已被证明可减少可卡因自我给药的条件范围。
Monoamine releasers constitute one class of candidate medications for treatment of cocaine abuse, and concurrent cocaine-versus-food choice procedures are potentially valuable as experimental tools to evaluate the efficacy and safety of candidate medications. This study assessed choice between cocaine and food by rhesus monkeys during treatment with five monoamine releasers that varied in selectivity to promote release of dopamine and norepinephrine (DA/NE) vs. serotonin (5HT) [m-fluoroamphetamine, (+)-phenmetrazine, (+)-methamphetamine, napthylisopropylamine and (±)-fenfluramine]. Rhesus monkeys (n=8) responded under a concurrent-choice schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0 – 0.1 mg/kg/inj, fixed-ratio 10 schedule). Cocaine choice dose-effect curves were determined daily during continuous seven-day treatment with saline or each test compound dose. During saline treatment, cocaine maintained a dose-dependent increase in cocaine choice, and the highest cocaine doses (0.032 – 0.1 mg/kg/inj) maintained almost exclusive cocaine choice. Efficacy of monoamine releasers to decrease cocaine choice corresponded to their pharmacological selectivity to release DA/NE vs. 5HT. None of the releasers reduced cocaine choice or promoted reallocation of responding to food choice to the same extent as substituting saline for cocaine. These results extend the range of conditions across which DA/NE-selective releasers have been shown to reduce cocaine self-administration.