在无脊椎动物模型中大麻素物理依赖和戒断的惊人分离

Wanhui Sheng, R. Raffa
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引用次数: 0

摘要

纯肠动物具有类似哺乳动物的神经递质系统,已被建立为一种新的体内神经药理学模型。在先前的研究中,暴露于大麻素受体(CB-R)激动剂WIN 55,212-2 1小时的涡虫在无药水中表现出戒断诱导的戒断,而在含药水中则没有。本研究的目的是扩展先前的工作,并进一步建立大麻素与涡虫的行为模型。结果表明:1)4种不同的CB-R拮抗剂(AM251、AM281、SLV319和SR144528)对2种不同CB-R拮抗剂(WIN 55,212-2和JWH251)诱导的身体依赖具有剂量相关阻断作用;2)相同的四种拮抗剂(AM251、AM281、SLV319或SR144528)均未引起停药;3)短波长紫外光(254 nm)可减弱戒断诱导的WIN 55,212-2戒断行为,而短波长紫外光(366 nm)可诱导中度戒断行为。结果证实使用涡虫模型作为一种简单而有力的方法来研究对大麻素激动剂的身体依赖的发展。紫外线照射的影响进一步证明了这一结果与受体有关。结果还提出了令人惊讶的建议,在方法的限制下,大麻素身体依赖的发展和拮抗剂诱导的沉淀戒断可能是涡虫中可分离的现象。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Surprising Separation of Cannabinoid Physical Dependence and Withdrawal in an Invertebrate Model
Planarians have mammalian-like neurotransmitter systems and have been established as a novel in vivo model for neuropharmacology. In previous research, planarians that have been exposed to the cannabinoid receptor (CB-R) agonist WIN 55,212-2 for 1 h displayed abstinence-induced withdrawal when tested in drug-free, but not in drug-containing, water. The goals of the present study were to extend previous work and to further establish a cannabinoid behavioral model with planarians. The results showed 1) four different CB-R antagonists (AM251, AM281, SLV319 and SR144528) dose-relatedly blocked development of physical dependence induced by two different CB-R agonists (WIN 55,212-2 and JWH251); 2) none of the same four antagonists (AM251, AM281, SLV319 or SR144528) precipitated withdrawal; 3) short wavelength (254 nm), but not long wavelength (366 nm), ultraviolet (UV) light attenuated abstinence-induced withdrawal from WIN 55,212-2, while short wavelength UV light induced moderate withdrawal behavior. The results confirm the use of a planarian model as a simple yet robust way to study development of physical dependence to cannabinoid agonists. The effect of UV irradiation adds to the evidence that the results are receptor-related. The results also give rise to the surprising suggestion, within the limitations of the methodology, that development of cannabinoid physical dependence and antagonist-induced precipitated withdrawal might be separable phenomena in planarians.
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