Effects of GBR 12909, WIN 35,428 and indatraline on cocaine self-administration and cocaine seeking in rats
Effects of GBR 12909, WIN 35,428 and indatraline on cocaine self-administration and cocaine seeking in rats
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DOI：
10.1007/s00213-001-0972-3
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发表时间：
2002-03-01
影响因子：
3.4
通讯作者：
Schenk, S
中科院分区：
文献类型：
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作者：
Schenk, S
理由：有人提出，减少可卡因自我给药或实验动物寻求可卡因的药物可能是治疗可卡因成瘾的有效药物疗法。先前的研究表明，多巴胺摄取抑制剂GBR 12909可能是这样一种候选药物，因为它可以减少可卡因的自我给药。其他研究表明，GBR 12909引起可卡因寻求，这可能限制其作为抗可卡因药物治疗的效用。目的：本研究旨在比较GBR 12909在减少可卡因自我给药和诱导可卡因寻求方面的效力。这些发现与可卡因类似物WIN 35,428和非特异性单胺摄取抑制剂indataline产生的效果进行了比较。方法：采用单次5 ~ 6 h每日自用可卡因的试验方案，获得剂量效应关系。实验前30 min分别用GBR 12909 （3.0 ~ 30.0 mg/kg）、WIN 35,428 （0.1 ~ 1.0 mg/kg）或吲哚啉（0.03 ~ 1.00 mg/kg）预处理大鼠。结果：GBR 12909和WIN 35,428降低了中、高剂量可卡因维持的反应，而茚丙林没有改变可卡因的剂量效应曲线。其他组的大鼠表明，这三种药物的预处理都恢复了已消失的可卡因服用行为，尽管茚丙林的效果不如GBR 12909或WIN 35,428。使用最高剂量的GBR 12909和WIN 35,428进行预处理可增强可卡因产生的药物寻求，但不受注射茚丙林的影响。低剂量的GBR 12909减少可卡因自我给药并没有产生药物寻求，但需要等量的WIN 35,428才能减少可卡因自我给药并引起药物寻求。结论：这些数据提示GBR 12909作为抗可卡因药物治疗的首选效果。然而，值得注意的是，这种药物可能会增强可卡因的能力，诱发戒断后寻求可卡因。
Rationale: It has been proposed that drugs that decrease cocaine self-administration or cocaine seeking by laboratory animals might be effective pharmacotherapies in the treatment of cocaine addiction. Previous studies have suggested that the dopamine uptake inhibitor, GBR 12909, might be such a candidate drug because it decreases cocaine self-administration. Other studies have shown that GBR 12909 elicits cocaine seeking, which might limit its utility as an anti-cocaine pharmacotherapy. Objectives: The present study sought to compare the potency of GBR 12909 in decreasing cocaine self-administration and in eliciting cocaine seeking. These findings were compared to effects produced by the cocaine analog, WIN 35,428 and the non-specific monoamine uptake inhibitor, indatraline. Methods: A within-session protocol was used to obtain the dose-effect relationship for cocaine self-administration in a single 5-6 h daily test session. Rats were pretreated with GBR 12909 (3.0-30.0 mg/kg), WIN 35,428 (0.1-1.0 mg/kg) or indatraline (0.03-1.00 mg/kg) 30 min prior to the test session. Results: GBR 12909 and WIN 35,428 decreased responding maintained by intermediate and high doses of cocaine but indatraline failed to alter the cocaine dose-effect curve. Other groups of rats demonstrated that pretreatment with all three drugs reinstated extinguished cocaine-taking behavior, although indatraline was less efficacious than either GBR 12909 or WIN 35,428. Cocaine-produced drug seeking was enhanced by pretreatment with the highest doses of GBR 12909 and WIN 35,428 but was unaffected by pretreatment with indatraline. A low dose of GBR 12909 that decreased cocaine self-administration failed to produce drug seeking but equal doses of WIN 35,428 were required to decrease cocaine self-administration and to elicit drug seeking. Conclusions: These data suggest a preferred profile of effects of GBR 12909 as an anti-cocaine pharmacotherapy. It is noted, however, that this drug might be expected to potentiate the ability of cocaine to elicit cocaine seeking following abstinence.