Schenk Susan
Department of Psychology, Texas A & M University, College Station, TX 77843, USA.
Psychopharmacology (Berl). 2002 Mar;160(3):263-70. doi: 10.1007/s00213-001-0972-3. Epub 2002 Jan 24.
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.
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.
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.
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.
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.
有人提出，能减少实验动物可卡因自我给药或觅药行为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，因为它能减少可卡因自我给药。其他研究表明，GBR 12909会引发觅药行为，这可能会限制其作为抗可卡因药物疗法的效用。
本研究旨在比较GBR 12909在减少可卡因自我给药和引发觅药行为方面的效力。将这些结果与可卡因类似物WIN 35,428和非特异性单胺摄取抑制剂因达曲林产生的效果进行比较。
采用单次每日5 - 6小时测试时段内的实验方案来获取可卡因自我给药的剂量效应关系。在测试时段前30分钟，给大鼠预先注射GBR 12909（3.0 - 30.0毫克/千克）、WIN 35,428（0.1 - 1.0毫克/千克）或因达曲林（0.03 - 1.00毫克/千克）。
GBR 12909和WIN 35,428减少了由中高剂量可卡因维持的反应，但因达曲林未能改变可卡因剂量效应曲线。其他几组大鼠表明，用这三种药物预处理均可恢复已消退的可卡因摄取行为，尽管因达曲林的效果不如GBR 12909或WIN 35,428。用最高剂量的GBR 12909和WIN 35,428预处理可增强可卡因引发的觅药行为，但因达曲林预处理对此无影响。低剂量的GBR 12909可减少可卡因自我给药，但不会引发觅药行为，而WIN 35,428减少可卡因自我给药和引发觅药行为则需要相同剂量。
这些数据表明GBR 12909作为抗可卡因药物疗法的一种优选效应特征。然而，需要注意的是，这种药物可能会增强可卡因在戒断后引发觅药行为的能力。
