Regional enhancement of cannabinoid CB1 receptor desensitization in female adolescent rats following repeated Δ9-tetrahydrocannabinol exposure
Regional enhancement of cannabinoid CB1 receptor desensitization in female adolescent rats following repeated Δ9-tetrahydrocannabinol exposure
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DOI：
10.1111/j.1476-5381.2010.00870.x
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发表时间：
2010-09-01
影响因子：
7.3
通讯作者：
Sim-Selley, Laura J.
中科院分区：
文献类型：
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作者：
Burston, James J.;Wiley, Jenny L.;Sim-Selley, Laura J.
背景和目的持续滥用大麻可能会导致青少年时期大脑重组的破坏。本研究的目的是确定青春期和成年大鼠在反复暴露于δ 9-四氢大麻酚（THC）后是否表现出脑大麻素（CB1）受体的差异适应。实验方法采用四氢大麻酚10 mg kg-1或四氢大麻酚对照剂，每天2次，连续用药9.5 d。随后评估CB1受体功能和密度。在所有脑区，四氢大麻酚处理产生CB1受体的脱敏和下调。虽然各组间的下调幅度没有差异，但在四氢大麻酚处理的雌性青春期大鼠大脑的大多数区域，脱敏程度明显提高。青春期雌性在前额皮质、海马、导水管周围灰质（PAG）和腹侧中脑表现出比成年雌性更大的脱敏性。相比之下，青春期男性在前额皮质、海马体和PAG中表现出较少的脱敏，与女性相反。除PAG外，性别差异仅在青少年中发现，女性前额皮质、纹状体、海马、PAG和腹侧中脑的脱敏程度更高。结论和意义这些结果表明，青少年女性的大脑可能特别容易受到大麻滥用对CB1受体信号的破坏。另外，脱敏性的增加可能反映了保护性适应。考虑到青春期大脑的广泛重组，这种破坏对内源性大麻素系统的成熟有潜在的长期影响。
BACKGROUND AND PURPOSEDisruption of the substantial re-organization of the brain during adolescence may be induced by persistent abuse of marijuana. The aim of this study was to determine whether adolescent and adult rats exhibit differential adaptation of brain cannabinoid (CB1) receptors after repeated exposure to Delta 9-tetrahydrocannabinol (THC).EXPERIMENTAL APPROACHRats of both ages and sexes were dosed with 10 mg kg-1 THC or vehicle twice daily for 9.5 days. Subsequently, CB1 receptor function and density were assessed.KEY RESULTSIn all brain regions, THC treatment produced desensitization and down-regulation of CB1 receptors. While the magnitude of down-regulation did not differ across groups, greater desensitization was evident in the brains of THC-treated female adolescent rats for most regions. Adolescent females showed greater desensitization than adult females in the prefrontal cortex, hippocampus, periaqueductal gray (PAG) and ventral midbrain. In contrast, adolescent males exhibited less desensitization in the prefrontal cortex, hippocampus and PAG, an effect opposite to that seen in females. With the exception of the PAG, sex differences were seen only in adolescents, with greater desensitization in the prefrontal cortex, striatum, hippocampus, PAG, and ventral midbrain of females.CONCLUSIONS AND IMPLICATIONSThese results suggest that the brains of adolescent females may be particularly vulnerable to disruption of CB1 receptor signalling by marijuana abuse. Alternatively, increased desensitization may reflect protective adaptation. Given the extensive re-organization of the brain during adolescence, this disruption has potential long-term consequences for maturation of the endocannabinoid system.