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δ9-四氢大麻酚和大麻素(CB1)受体基因表达对小鼠的神经行为影响。

Neurobehavioral effects of delta 9-THC and cannabinoid (CB1) receptor gene expression in mice.

作者信息

Onaivi E S, Chakrabarti A, Gwebu E T, Chaudhuri G

机构信息

Department of Pharmacology, Meharry Medical College, Nashville, TN 37208, USA.

出版信息

Behav Brain Res. 1995 Dec 14;72(1-2):115-25. doi: 10.1016/0166-4328(96)00139-8.

DOI:10.1016/0166-4328(96)00139-8
PMID:8788864
Abstract

The differential sensitivity following the administration of delta 9-THC to 3 mouse strains, C57BL/6, DBA/2 and ICR mice, indicated that some of the neurobehavioral changes may be attributable to genetic differences. The objective of this study was to determine the extent to which the cannabinoid (CB1) receptor is involved in the observed behavioral changes following delta 9-THC administration. This objective was addressed by experiments using: (1) DNA-PCR and reverse PCR; (2) systemic administration of delta 9-THC, and; (3) intracerebral microinjection of delta 9-THC. The site specificity of action of delta 9-THC in the brain was determined using stereotaxic surgical approaches. The intracerebral microinjection of delta 9-THC into the nucleus accumbens was found to induce catalepsy, while injection of delta 9-THC into the central nucleus of amygdala resulted in the production of an anxiogenic-like response. Although the DNA-PCR data indicated that the CB1 gene appeared to be identical and intronless in all 3 mouse strains, the reverse PCR data showed two additional distinct CB1 mRNAs in the C57BL/6 mouse which also differed in pain sensitivity and rectal temperature changes following the administration of delta 9-THC. It is suggested that the diverse neurobehavioral alterations induced by delta 9-THC may not be mediated solely by the CB1 receptors in the brain and that the CB1 genes may not be uniform in the mouse strains.

摘要

给C57BL/6、DBA/2和ICR这3种小鼠品系注射Δ9-四氢大麻酚(delta 9-THC)后的差异敏感性表明,某些神经行为变化可能归因于基因差异。本研究的目的是确定大麻素(CB1)受体在注射Δ9-THC后所观察到的行为变化中所起作用的程度。通过以下实验实现该目的:(1)DNA-PCR和逆转录PCR;(2)全身性注射Δ9-THC;以及(3)脑内微量注射Δ9-THC。使用立体定向手术方法确定了Δ9-THC在脑内作用的位点特异性。发现向伏隔核脑内微量注射Δ9-THC会诱发僵住症,而向杏仁核中央核注射Δ9-THC则会产生类似焦虑的反应。尽管DNA-PCR数据表明CB1基因在所有3种小鼠品系中似乎是相同且无内含子的,但逆转录PCR数据显示C57BL/6小鼠中有另外两种不同的CB1 mRNA,在注射Δ9-THC后,它们在疼痛敏感性和直肠温度变化方面也存在差异。提示Δ9-THC诱导的多种神经行为改变可能并非仅由脑内的CB1受体介导,且CB1基因在小鼠品系中可能并不一致。

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