Methoxetamine, a ketamine derivative, produced Conditioned place preference and was self-administered by rats: Evidence of its abuse potential
Methoxetamine, a ketamine derivative, produced Conditioned place preference and was self-administered by rats: Evidence of its abuse potential
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DOI：
10.1016/j.pbb.2015.03.007
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发表时间：
2015-06-01
影响因子：
3.6
通讯作者：
Cheong, Jae Hoon
中科院分区：
文献类型：
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作者：
Botanas, Chrislean Jun;de la Pena, June Bryan;Cheong, Jae Hoon
甲氧西胺 (MXE) 是一种 N-甲基-D-天冬氨酸 (NMDA) 受体拮抗剂，其化学和药理学与氯胺酮相似。最近，有许多关于其在人类中使用/误用的报道，导致严重甚至致命的后果。尽管有这些报告，MXE 在许多国家并未受到控制或监管，部分原因可能是缺乏关于其滥用潜力的科学证据。因此，在本研究中，我们通过 Sprague-Dawley 大鼠的条件性位置偏好 (CPP) 和自我给药 (SA) 测试评估了 MXE 的滥用潜力（奖励和强化效应）。此外，还分析了 CPP 调节阶段的运动活动。使用氯胺酮作为参考药物。 MXE（2.5 和 5 mg/kg）在大鼠中诱导显着的 CPP，其效果与氯胺酮（5 mg/kg）相当。有趣的是，MXE 不会产生任何运动改变，而氯胺酮会降低大鼠的运动活动。在 SA 测试中，大鼠表现出适度的自我给药 MXE（0.25、0.5、1.0 mg/kg/输注），而氯胺酮（0.5 mg/kg/输注）则表现出强烈的自我给药。这些结果表明，MXE 与氯胺酮类似，对大鼠具有奖励和强化作用。目前的研究强烈表明 MXE 有可能被人类滥用。此外，MXE 和氯胺酮对运动活动和自我给药率的不同影响表明这些药物的精神药理学作用可能在某些方面存在差异。更重要的是，这项研究提倡对MXE及其相关物质进行仔细监测和及时监管。 (C) 2015 Elsevier Inc. 保留所有权利。
Methoxetamine (MXE) is an N-methyl-D-aspartate (NMDA) receptor antagonist that is chemically and pharmacologically similar to ketamine. Recently, there have been many reports regarding its use/misuse in humans which have resulted in serious or even fatal outcomes. Despite these reports, MXE is not controlled or regulated in many countries which may be partly due to the lack of scientific evidence regarding its abuse potential. Thus, in the present study we evaluated the abuse potential (rewarding and reinforcing effects) of MXE through the conditioned place preference (CPP) and self-administration (SA) tests in Sprague-Dawley rats. In addition, locomotor activity during the conditioning phase of the CPP was also analyzed. Ketamine was used as a reference drug. MXE (2.5 and 5 mg/kg) induced significant CPP in rats, an effect comparable to that of ketamine (5 mg/kg). Interestingly, MXE did not produce any locomotor alterations while ketamine decreased the locomotor activity of rats. In the SA test, rats showed modest self-administration of MXE (0.25, 0.5, 1.0 mg/kg/infusion), while ketamine (0.5 mg/kg/infusion) was robustly self-administered. These results demonstrate that MXE, similar to ketamine, has rewarding and reinforcing effects in rats. The present study strongly suggests that MXE has a potential for human abuse. In addition, the discrepant effects of MXE and ketamine on locomotor activity and rate of self-administration propose that the psychopharmacological effects of these drugs may diverge in some aspects. More importantly, this study advocates the careful monitoring and prompt regulation of MXE and its related substances. (C) 2015 Elsevier Inc. All rights reserved.