Differential Developmental Trajectories for CB1 Cannabinoid Receptor Expression in Limbic/Associative and Sensorimotor Cortical Areas
Differential Developmental Trajectories for CB1 Cannabinoid Receptor Expression in Limbic/Associative and Sensorimotor Cortical Areas
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DOI：
10.1002/syn.20844
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发表时间：
2011-04-01
期刊：
影响因子：
2.3
通讯作者：
Tseng, Kuei Y.
中科院分区：
文献类型：
--
作者：
Heng, Lijun;Beverley, Joel A.;Tseng, Kuei Y.
青少年时期使用大麻会增加患精神分裂症和其他疾病的风险。神经元基础尚不清楚，但涉及前额皮质机制。在这里，我们通过评估幼年大鼠（出生后25天，P25）、青春期大鼠（P40）和成年大鼠（P70）前额叶和其他皮质区域CB1大麻素受体的表达和功能来研究内源性大麻素系统的发育变化。总体而言，CB1受体在幼体皮层的表达量最高，随后逐渐下降至成年水平。然而，CB1受体的表达在不同的皮质区域遵循不同的发育轨迹。在内侧前额叶和其他边缘/相关区域观察到CB1表达最明显和进行性下降。相比之下，感觉运动皮层的主要变化仅发生在P40之后。我们还评估了CB1受体功能的电生理测量，发现前额皮质中CB1依赖性突触传递抑制遵循与受体表达相同的发育轨迹。总之，这些发现表明CB1受体介导的信号在发育过程中减少，但在边缘/联合与感觉运动系统中受到不同的调节。因此，在青春期使用大麻可能会对边缘/联想和感觉运动皮层回路产生不同的影响。中文信息学报（英文版），2011。(C) 2010 Wiley-Liss, Inc。
Cannabis use during adolescence is associated with an increased risk for schizophrenia and other disorders. The neuronal basis is unclear, but prefrontal cortical mechanisms have been implicated. Here, we investigated developmental changes in the endocannabinoid system by assessing expression and function of the CB1 cannabinoid receptor in prefrontal and other cortical areas in juvenile (postnatal day 25, P25), adolescent (P40), and adult (P70) rats. Overall, the expression of CB1 receptors in the cortex is highest in juveniles and drops thereafter toward adult levels. However, CB1 receptor expression follows distinct developmental trajectories in different cortical areas. The most pronounced and progressive decrease in CB1 expression was observed in medial prefrontal and other limbic/associative regions. In contrast, major changes in sensorimotor cortices occurred only after P40. We also assessed electrophysiological measures of CB1 receptor function and found that CB1-dependent inhibition of synaptic transmission in the prefrontal cortex follows the same developmental trajectory as observed for receptor expression. Together, these findings indicate that CB1 receptor-mediated signaling decreases during development but is differentially regulated in limbic/associative vs. sensorimotor systems. Therefore, cannabis use during adolescence likely differentially affects limbic/associative and sensorimotor cortical circuits. Synapse 65:278-286, 2011. (C) 2010 Wiley-Liss, Inc.