Lack of behavioral sensitization after repeated exposure to THC in mice and comparison to methamphetamine.
Lack of behavioral sensitization after repeated exposure to THC in mice and comparison to methamphetamine.
复制标题
小鼠反复接触 THC 后缺乏行为敏感性，并与甲基苯丙胺进行比较。
DOI：
10.1007/s00213-007-0811-2
复制
发表时间：
2007
影响因子：
3.4
通讯作者：
Lichtman,AronH
中科院分区：
文献类型：
--
作者：
Varvel,StephenA;Martin,BillyR;Lichtman,AronH
合理最近的证据支持成瘾的激励-敏化模型，在该模型中，反复刺激神经奖赏回路会导致中脑边缘多巴胺能活动的长期敏化。这一现象已经在许多滥用药物中得到了证明，最常见的是通过测量药物对运动活动的逐渐增强的激活效应，认为这反映了潜在的神经敏化。大麻素，特别是Δ-9-四氢大麻酚(THC)是否在该模型中产生类似的作用尚有争议，文献中证据不一。目的本实验旨在确定反复暴露于THC后是否能在小鼠中建立行为敏化。方法以甲基苯丙胺反复给药致敏为阳性对照。方法采用肿瘤研究所(ICR)小鼠，观察THC或甲基苯丙胺急性间歇给药对小鼠运动能力的影响。关于THC的其他实验采用了一种剂量方案，增加了注射次数，控制了行为耐受性，检查了行为的不同方面，并使用了不同的物种(Spraogue-Dawley大鼠)。结果甲基苯丙胺和THC都显著增加了活性。甲基苯丙胺间歇治疗后，观察到强烈的剂量依赖性致敏作用，但与THC无关。此外，在任何不同的方案中都没有发现对THC影响的行为敏化的证据。结论这些数据表明重复THC治疗比其他滥用药物产生行为敏化的可能性更小。这一现象似乎只有在非常特殊的条件下才会发生，这使人对其与长期吸食大麻的人的相关性产生怀疑。
RationaleRecent evidence has provided support for the incentive-sensitization model of addiction, where repeated stimulation of neural reward circuits leads to a long-lasting sensitization of mesolimbic dopaminergic activity. This phenomenon has been demonstrated with many drugs of abuse, most often by measuring progressively increased activating effects of drugs on locomotor activity, thought to reflect an underlying neural sensitization. Whether cannabinoids, and in particular Δ9-tetrahydrocannabinol (THC), produce similar effects in this model is somewhat controversial, with mixed evidence in the literature.ObjectivesThese experiments were conducted to determine whether behavioral sensitization could be established in mice after repeated exposure to THC. Sensitization to repeated methamphetamine treatment was used as a positive control.MethodsThe effects of acute and repeated intermittent (every 3–4 days) treatment with THC or methamphetamine on locomotor activity were determined in Institute of Cancer Research (ICR) mice. Additional experiments with THC employed a dosing regimen that increased the number of injections, controlled for behavioral tolerance, examined different aspects of behavior, and used a different species (Sprague–Dawley rats).ResultsBoth methamphetamine and THC acutely increased activity. A robust dose-dependent sensitization was observed after intermittent treatment with methamphetamine but not with THC. Additionally, no evidence for behavioral sensitization to the effects of THC was found with any of the various protocols.ConclusionThese data suggest that repeated THC treatment is less likely to produce behavioral sensitization than are other drugs of abuse. It appears that this phenomenon may only occur under very particular conditions, which raises doubts about its relevance to chronic cannabis users.