Acute opioid but not benzodiazepine dependence in rats responding for intracranial self-stimulation
Acute opioid but not benzodiazepine dependence in rats responding for intracranial self-stimulation
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DOI：
10.1007/s002130050050
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发表时间：
2000-02-01
影响因子：
3.4
通讯作者：
Holtzman, SG
中科院分区：
文献类型：
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作者：
Easterling, KW;Plovnick, RM;Holtzman, SG
理由：用单剂量吗啡或相关阿片类药物进行四小时预处理，可使颅内自我刺激 (ICSS) 反应的大鼠对纳曲酮的速率降低作用敏感，表明拮抗剂可促使急性阿片类药物依赖性戒断。目的：确定吗啡预处理的大鼠在 ICSS 渐进比例 (PR) 方案下是否观察到对纳曲酮的过敏，并确定苯二氮卓类药物的急性预处理是否会产生与氟马西尼类似的过敏。方法：训练内侧前脑束内有电极的大鼠在 ICSS PR 计划下做出反应，其中 250 毫秒刺激所需的反应数量从 1 次开始，然后逐渐增加。如果 30 秒内没有响应，则响应要求为单个响应，并且在操作上定义了断点。结果：用 3.0 mg/kg 或 5.6 mg/kg 吗啡预处理（4 小时）可降低纳曲酮的 ED 值，使反应率从 18+/-6.7 mg/kg 分别降低至 0.021+/-0.006 mg/kg 和 0.006+/-0.001 mg/kg。断点的变化通常与响应率的变化同时发生。相比之下，用行为活性剂量的苯二氮卓类利眠宁（30 mg/kg 和 100 mg/kg）或地西泮（3.0 mg/kg 和 10 mg/kg）进行 4 至 24 小时预处理，并没有显着改变对氟马西尼（1.0-30 mg/kg）作用的敏感性。结论：这些结果表明 PR ICSS 为大鼠药物测试提供了稳定的行为基线，并将急性阿片类药物依赖现象的普遍性扩展到该程序。没有类似的证据表明急性苯二氮卓类依赖，这表明阿片类药物和苯二氮卓类激动剂引发身体依赖状态下的适应性变化的方式存在差异。
Rationale: Four-hour pretreatment with a single dose of morphine or related opioids sensitizes rats responding for intracranial self-stimulation (ICSS) to the rate-decreasing effect of naltrexone, indicative of antagonist-precipitated withdrawal from acute opioid dependence. Objectives: To determine whether sensitization to naltrexone could be observed in morphine-pretreated rats responding under a progressive ratio (PR) schedule of ICSS and to determine whether acute pretreatment with benzodiazepines produces similar sensitization to flumazenil. Methods: Rats with an electrode in the medial forebrain bundle were trained to respond under an ICSS PR schedule, in which the number of responses required for a 250-ms stimulus started at one, then increased gradually. If no responding occurred for 30 s, the response requirement revel ted to a single response and the break point was operationally defined. Results: Pretreatment (4-h) with 3.0 mg/kg or 5.6 mg/kg morphine reduced the ED,, values of naltrexone for decreasing response rate fi om 18+/-6.7 mg/kg to 0.021+/-0.006 mg/kg and 0.006+/-0.001 mg/kg, respectively. Changes in break point usually paralleled changes in response rate. In contrast, 4- to 24-h pretreatment with the benzodiazepines chlordiazepoxide (30 mg/kg and 100 mg/kg) or diazepam (3.0 mg/kg and 10 mg/kg), behaviorally-active doses, did not significantly alter sensitivity to the effects of flumazenil (1.0-30 mg/kg). Conclusions: These results show that PR ICSS provides a stable behavioral baseline for testing drugs in rats and extend to this procedure the generality of the phenomenon of acute opioid dependence. There was no comparable evidence of acute benzodiazepine dependence, suggesting that there are differences in the ways that opioid and benzodiazepine agonists initiate the adaptive changes that underlie the state of physical dependence.