Pretreatment with the dopamine agonist 7‐OH‐DPAT shifts the cocaine self‐administration dose‐effect function to the left under different schedules in the rat
Pretreatment with the dopamine agonist 7‐OH‐DPAT shifts the cocaine self‐administration dose‐effect function to the left under different schedules in the rat
复制标题
多巴胺激动剂 7-OH-DPAT 预处理使大鼠不同方案下可卡因自我给药剂量效应函数向左移动
作者：
S. Caine;G. Koob
本研究检验了多巴胺激动剂7-羟基-N，N-二-正丙基-2-氨基四氢化萘（7-OH-DPAT）给药使可卡因自我给药剂量效应函数向左偏移，而不是产生非特异性效应或专门增强高剂量可卡因的速率降低效应的假设。在固定比例或渐进比例方案下，允许大鼠静脉内自我施用可卡因、7-OH-DPAT或可卡因和7-OH-DPAT的组合。在固定比例方案下的其他试验中，可卡因自我给药后皮下预处理7-OH-DPAT。可卡因剂量-效应函数通过改变测试会话之间或单个会话内的可卡因的单位剂量来获得。静脉注射7-OH-DPAT（1-4 μg）减少了固定比例方案下训练剂量可卡因（0.25 mg）的自我给药，但未能将固定比例或渐进比例方案下整个可卡因自我给药剂量效应函数向左偏移。在这些时间表下，7-OH-DPAT单独维持静脉内自我给药，但在渐进比时间表下，相对于可卡因，产生浅的自我给药剂量-效应函数。与静脉内7-OH-DPAT相比，s.c.用7-OH-DPAT（0.1-0.4 mg/kg）预处理不仅减少了训练剂量的可卡因的自我给药，而且降低了固定比例时间表下可卡因的最小有效剂量，产生可卡因自我给药剂量-效应函数的左移;这些效应与可卡因剂量是否在疗程之间或单一疗程内变化无关。同样，在多个时间表下，其中响应由可卡因和食物中的替代成分维持，s.c.用7-OH-DPAT预处理增加了剂量-效应函数的上升肢上的可卡因剂量的自我给药，并减少了下降肢上的可卡因剂量的自我给药，同时均匀地降低了对食物的反应。这些观察结果表明，7− OH-DPAT预处理增强了可卡因的增强特性，而不是产生非特异性效应或仅增强高剂量自我给药可卡因的速率降低效应。
This study tested the hypothesis that administration of the dopamine agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) shifts the cocaine self-administration dose-effect function to the left, rather than producing nonspecific effects or exclusively enhancing the rate-decreasing effects of high doses of cocaine. Under fixed-ratio or progressive-ratio schedules, rats were allowed to intravenously self-administer cocaine, 7-OH-DPAT, or a combination of cocaine and 7-OH-DPAT. In additional tests under fixed-ratio schedules, cocaine self-administration followed subcutaneous pretreatment with 7-OH-DPAT. Cocaine dose-effect functions were obtained by varying the unit dose of cocaine either between test sessions or within a single session. Intravenous 7-OH-DPAT (1–4 μg) decreased self-administration of the training dose of cocaine (0.25 mg) under a fixed-ratio schedule, but failed to shift the entire cocaine self-administration dose effect function to the left under fixed-ratio or progressive-ratio schedules. 7-OH-DPAT alone maintained i.v. self-administration under these schedules, but produced a shallow self-administration dose-effect function, relative to cocaine, under the progressive-ratio schedule. In contrast to intravenous 7-OH-DPAT, s.c. pretreatment with 7-OH-DPAT (0.1–0.4 mg/kg) not only decreased self-administration of the training dose of cocaine but also lowered the minimum effective dose of cocaine under fixed-ratio schedules, producing a shift to the left of the cocaine self-administration dose-effect function; these effects were independent of whether the dose of cocaine was varied between sessions or within a single session. Likewise under a multiple schedule, in which responding was maintained by cocaine and food in alternate components, s.c. pretreatment with 7-OH-DPAT increased self-administration of the dose of cocaine on the ascending limb of the dose-effect function and decreased self-administration of doses of cocaine on the descending limb, while uniformly decreasing responding for food. These observations suggest that pretreatment with 7− OH-DPAT enhances the reinforcing properties of cocaine rather than producing nonspecific effects or enhancing exclusively the rate-decreasing effects of high doses of self-administered cocaine.