Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Δ9-tetrahydrocannabinol
Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Δ9-tetrahydrocannabinol
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DOI：
10.1007/s00213-007-0721-3
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发表时间：
2007-06-01
影响因子：
3.4
通讯作者：
Karl, T.
中科院分区：
文献类型：
--
作者：
Boucher, A. A.;Arnold, J. C.;Karl, T.
理由：大麻的使用可能导致精神分裂症，特别是如果个人有这种精神障碍的遗传易感性。人类和动物研究表明，神经调节蛋白1 （Nrg1）是精神分裂症的易感基因。目的研究Nrg1基因的功能障碍是否会调节脑卒中的行为效应。9-四氢大麻酚（THC），大麻的主要精神药物成分。材料与方法采用急性四氢大麻酚（0、5、10 mg/kg）治疗Nrg1跨膜结构域敲除小鼠（Nrg1 HET）。测试前30分钟，采用开放场（OF）、孔板（HB）、光暗（LD）、升高加迷宫（EPM）、社会互动（SI）和脉冲前抑制（PPI）测试。结果Nrg1 HET小鼠在运动活动、探索和焦虑方面的基线行为存在差异。更重要的是，与野生型（WT）小鼠相比，它们对THC的运动抑制作用更敏感。此外，Nrg1 heet小鼠比WT小鼠表达了更大的thc诱导的% PPI增强。四氢大麻酚对焦虑相关行为的影响是任务依赖的，Nrg1 HET小鼠在LD中比WT小鼠更容易受到四氢大麻酚的焦虑作用，但在EPM、SI和of测试中则没有。结论Nrg1 HET小鼠对四氢大麻酚在一系列不同行为中的急性作用更敏感，包括那些模拟精神分裂症症状的行为。似乎精神分裂症相关的神经调节蛋白1基因的变异改变了对大麻素行为影响的敏感性。
Rationale Cannabis use may precipitate schizophrenia especially if the individual has a genetic vulnerability to this mental disorder. Human and animal research indicates that neuregulin 1 (Nrg1) is a susceptibility gene for schizophrenia. Objectives The aim of this study was to investigate whether dysfunction in the Nrg1 gene modulates the behavioural effects of.9-tetrahydrocannabinol (THC), the major psychotropic component of cannabis. Materials and methods Heterozygous Nrg1 transmembranedomain knockout mice (Nrg1 HET) were treated with acute THC (0, 5 or 10 mg/kg i.p.) 30 min before being tested using open field (OF), hole board (HB), light-dark (LD), elevated plus maze (EPM), social interaction (SI) and prepulse inhibition (PPI) tests. Results Nrg1 HET mice showed differences in baseline behaviour with regard to locomotor activity, exploration and anxiety. More importantly, they were more sensitive to the locomotor suppressant actions of THC compared to wild type- like (WT) mice. In addition, Nrg1 HET mice expressed a greater THC-induced enhancement in % PPI than WT mice. The effects of THC on anxiety-related behaviour were task-dependent, with Nrg1 HET mice being more susceptible than WT mice to the anxiogenic effects of THC in LD, but not in the EPM, SI and OF tests. Conclusions Nrg1 HET mice were more sensitive to the acute effects of THC in an array of different behaviours including those that model symptoms of schizophrenia. It appears that variation in the schizophrenia-related neuregulin 1 gene alters the sensitivity to the behavioural effects of cannabinoids.