Brain regional differences in CB1 receptor adaptation and regulation of transcription.
Brain regional differences in CB1 receptor adaptation and regulation of transcription.
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DOI：
10.1016/j.lfs.2012.08.023
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发表时间：
2013-03-19
期刊：
影响因子：
6.1
通讯作者：
Sim-Selley, L. J.
中科院分区：
文献类型：
--
作者：
Lazenka, M. F.;Selley, D. E.;Sim-Selley, L. J.
Cannabinoid CB1 receptors (CB1Rs) are expressed throughout the brain and mediate the central effects of cannabinoids, including Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana. Repeated THC administration produces tolerance to cannabinoid-mediated effects, although the magnitude of tolerance varies by effect. Consistent with this observation, CB1R desensitization and downregulation, as well induction of immediate early genes (IEGs), varies by brain region. Zif268 and c-Fos are induced in the forebrain after acute THC administration. Phosphorylation of the cAMP response-element binding protein (CREB) is increased in a region-specific manner after THC administration. Results differ between acute versus repeated THC injection, and suggest that tolerance to IEG activation might develop in some regions. Repeated THC treatment produces CB1R desensitization and downregulation in the brain, although less adaption occurs in the striatum as compared to regions such as the hippocampus. Repeated THC treatment also induces expression of ΔFosB, a very stable isoform of FosB, in the striatum. Transgenic expression of ΔFosB in the striatum enhances the rewarding effects of several drugs, but its role in THC-mediated effects is not known. The inverse regional relationship between CB1R desensitization and ΔFosB induction suggests that these adaptations might inhibit each other, although this possibility has not been investigated. The differential regional expression of individual IEGs by acute or repeated THC administration suggests that regulation of target genes and effects on CB1R signaling will contribute to the behavioral effects of THC.
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影响因子：
8.2
作者：
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通讯作者：
Fisone, Gilberto
影响因子：
3.6
作者：
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通讯作者：
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DOI：
10.1124/jpet.102.044446
发表时间：
2003-05-01
影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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