Anxiolytic-like actions of buspirone in a runway model of intravenous cocaine self-administration
Anxiolytic-like actions of buspirone in a runway model of intravenous cocaine self-administration
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DOI：
10.1016/j.pbb.2006.09.007
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发表时间：
2006-10-01
影响因子：
3.6
通讯作者：
Bernardi, Rick E.
中科院分区：
文献类型：
--
作者：
Ettenberg, Aaron;Bernardi, Rick E.
在我们实验室以前的工作中，已经观察到大鼠穿越一条笔直的小巷以获得IV可卡因的奖励，从而对进入目标箱产生矛盾心理。在试验过程中，动物反复跑向目标框，在入口处停下来，然后退回到开始框。这种独特的撤退行为模式已经被证明反映了一种形式的“接近-回避冲突”，这种冲突源于受试者与目标框同时发生的积极（可卡因奖励）和消极（可卡因引起的焦虑）关联。丁螺环酮是一种部分5-HT 1A激动剂，据报道在临床上产生抗焦虑样作用，但在使用动物受试者进行的焦虑实验测试中结果不一。由于大多数冲突/焦虑的动物试验采用足部电击（一种相对较强的厌恶性刺激），因此有必要确定丁螺环酮是否会改变在经过良好训练的动物中观察到的更微妙的接近-回避冲突，这些动物每天单次静脉注射1.0 mg/kg可卡因。跑道试验包括每天一次的试验，一直持续到出现一致的接近-回避后退。然后在跑道试验前30分钟，用溶剂和三种剂量的丁螺环酮（0.0、1.0、2.5或5.0 mg/kg IP）中的一种对每只动物进行预处理。以平衡方式继续测试，直到所有大鼠经历了丁螺环酮的每个剂量，每个测试日之间进行3天的仅可卡因试验。在每次试验中表现出的撤退次数作为该试验中存在的接近-回避冲突的指数。结果清楚地表明，丁螺环酮（在两个较高剂量下）减弱了接近IV可卡因目标盒的动物的退缩行为-这一作用与其在临床中的抗焦虑样作用一致。(c)2006年爱思唯尔公司All rights reserved.
In previous work from our laboratory, rats traversing a straight alley for a reward of IV cocaine have been observed to develop ambivalence about entering the goal box. Over trials, animals repeatedly run toward the goal box, stop at the entry point, and then retreat back toward the start box. This unique pattern of retreat behavior has been shown to reflect a form of "approach-avoidance conflict" that stems from the subjects' concurrent positive (cocaine reward) and negative (cocaine-induced anxiety) associations with the goal box. Buspirone, a partial 5-HT1A agonist, has been reported to produce anxiolytic-like actions in the clinic, but has had mixed results in experimental tests of anxiety using animal subjects. Since most animal tests of conflict/anxiety employ the administration of foot-shock - a relatively strong aversive stimulus - it was of interest to determine whether buspirone would alter the more subtle approach-avoidance conflict observed in well-trained animals running a straight alley for single daily injections of 1.0 mg/kg IV cocaine. Runway testing consisted of single daily trials that continued until consistent approach-avoidance retreats were exhibited. Each animal was then pretreated 30 min prior to runway testing with vehicle and one of three doses of buspirone (0.0, 1.0, 2.5 or 5.0 mg/kg IP). Testing continued in a counterbalanced manner until all rats had experienced each dose of buspirone with 3 days of cocaine-only trials between each test day. The number of retreats exhibited on each trial served as an index of the approach-avoidance conflict present on that trial. Results clearly demonstrated that buspirone (at the two higher doses) attenuated the retreat behavior of animals approaching a goal box for IV cocaine - an action consistent with its anxiolytic-like actions in the clinic. (c) 2006 Elsevier Inc. All rights reserved.