Department of Psychology and Office for Training, Research, and Education in the Sciences, California State University San Marcos, 333 S. Twin Oaks Valley Road, San Marcos, CA 92096-0001, USA.
Department of Psychology and Office for Training, Research, and Education in the Sciences, California State University San Marcos, 333 S. Twin Oaks Valley Road, San Marcos, CA 92096-0001, USA.
Behav Brain Res. 2020 Jan 27;378:112271. doi: 10.1016/j.bbr.2019.112271. Epub 2019 Oct 5.
Ketamine is a dissociative anesthetic first developed in the 1960s but is increasingly used at subanesthetic doses for both clinical and non-clinical purposes. There is evidence from human recreational users of compulsive use and addiction. Sensitization is an increase in an effect of a drug with repeated use that is thought to be important in the development of addiction. Research on psychomotor stimulants has shown the development of sensitization in laboratory animals to be modified by factors that influence addiction. In the current paper we describe four experiments on the development of sensitization in laboratory rats aimed at determining if ketamine sensitization is also influenced by factors thought to be important in addiction. Adult, male Sprague-Dawley rats received ketamine (5, 10, 20 or 50 mg/kg i.p.) for five or more days and the development of locomotor sensitization was followed. Experiment 1 examined the ability of low doses of ketamine to produce sensitization and found sensitization at 5, 10 and 20 mg/kg. Experiment 2 examined the influence of environmental context and found that ketamine sensitization (20 mg/kg) was greater when administration occurred in a novel environment (the experimental apparatus) than in home cages. Experiment 3 found that ketamine sensitization (20 mg/kg) did not occur when animals were housed in social isolation but occurred readily in pair-housed animals. Finally, Experiment 4 found that ketamine sensitization (20 or 50 mg/kg) was similar whether drug was administered daily or at 3-day intervals. Together, the results demonstrate that ketamine sensitization is robust and reliable, occurring under a variety of circumstances. Moreover, ketamine sensitization is influenced by factors that influence the development of addiction in humans. The current results may lead to a better understanding of ketamine abuse and addiction and may help inform clinical use of the drug.
氯胺酮是一种分离性麻醉剂，于 20 世纪 60 年代首次开发，但越来越多地以亚麻醉剂量用于临床和非临床用途。有证据表明，人类娱乐性使用者会强迫使用并上瘾。敏化作用是指随着药物的重复使用，药物的效果增加，这被认为是成瘾发展的重要因素。对精神运动兴奋剂的研究表明，实验室动物的敏化作用发展可以通过影响成瘾的因素来改变。在当前的论文中，我们描述了四项旨在确定氯胺酮敏化作用是否也受到被认为与成瘾有关的重要因素影响的实验室大鼠敏化作用发展实验。成年雄性 Sprague-Dawley 大鼠接受氯胺酮（5、10、20 或 50mg/kg 腹腔注射）五天以上，并跟踪运动敏化作用的发展。实验 1 检验了低剂量氯胺酮产生敏化作用的能力，发现 5、10 和 20mg/kg 时出现敏化作用。实验 2 检验了环境背景的影响，发现当药物在新环境（实验仪器）中而不是在笼中给药时，氯胺酮敏化作用（20mg/kg）更大。实验 3 发现，当动物被隔离饲养时，氯胺酮敏化作用（20mg/kg）不会发生，但在成对饲养的动物中很容易发生。最后，实验 4 发现，当药物每日或每隔 3 天给予时，氯胺酮敏化作用（20 或 50mg/kg）相似。总之，这些结果表明氯胺酮敏化作用是强大而可靠的，在各种情况下都会发生。此外，氯胺酮敏化作用受到影响人类成瘾发展的因素的影响。目前的结果可能有助于更好地理解氯胺酮滥用和成瘾，并可能有助于为该药物的临床应用提供信息。
