Prefrontal cortical distribution of muscarinic M2 and cannabinoid-1 (CB1) receptors in adult male mice with or without chronic adolescent exposure to Δ9-tetrahydrocannabinol.
Prefrontal cortical distribution of muscarinic M2 and cannabinoid-1 (CB1) receptors in adult male mice with or without chronic adolescent exposure to Δ9-tetrahydrocannabinol.
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成年雄性小鼠中毒蕈碱 M2 和大麻素 1 (CB1) 受体的前额皮质分布，有或没有慢性青少年暴露于 α9-四氢大麻酚。
DOI：
10.1093/cercor/bhac024
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Pickel,VirginiaM
中科院分区：
文献类型：
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作者：
Garzón,Miguel;Chan,June;Mackie,Ken;Pickel,VirginiaM
大麻的主要精神活性化合物，Δ 9-四氢大麻酚（Δ9-THC）的慢性青少年管理，产生适应性变化，在成人的社会和认知功能维持的前边缘前额叶皮层（PL-PFC）。PL-PFC神经元中的记忆和学习过程可以通过胆碱能毒蕈碱-2受体（M2 R）调节，并通过Δ9-THC靶向的大麻素-1受体（CB 1 R）的激活来调节。因此，青春期长期暴露于Δ9-THC可能会改变接受CB 1 R终末的PL-PFC神经元中M2 R的表达和/或分布。我们通过在成年C57 BL/6 J雄性小鼠中使用电子显微镜双CB 1 R和M2 R免疫标记来验证这一假设，这些小鼠在青春期接受了媒介物或递增剂量的Δ9-THC。在溶剂对照组中，CB 1 R免疫标记主要定位于几乎没有M2 R的轴突轮廓，但通常与M2 R免疫反应性树突和树突棘并列。树突从CB 1 R标记的或未标记的终端接收输入，而棘仅从缺乏CB 1 R的轴突终端接收不对称突触。青少年Δ9-THC显著增加质膜M2 R-免疫金密度，仅在接受CB 1 R标记终末输入的大树突中。相比之下，在Δ9-THC处理的成年小鼠的小棘中，细胞质M2 R-免疫金密度降低。我们得出结论，青春期CB 1 Rs的Δ9-THC参与增加了PL-PFC大近端树突中M2 R质膜的积累，并降低了PL-PFC小棘中M2 R胞质的表达。
Chronic adolescent administration of marijuana’s major psychoactive compound, ∆9-tetrahydrocannabinol (Δ9-THC), produces adaptive changes in adult social and cognitive functions sustained by prelimbic prefrontal cortex (PL-PFC). Memory and learning processes in PL-PFC neurons can be regulated through cholinergic muscarinic-2 receptors (M2R) and modulated by activation of cannabinoid-1 receptors (CB1Rs) targeted by Δ9-THC. Thus, chronic exposure to Δ9-THC during adolescence may alter the expression and/or distribution of M2Rs in PL-PFC neurons receiving CB1R terminals. We tested this hypothesis by using electron microscopic dual CB1R and M2R immunolabeling in adult C57BL/6 J male mice that had received vehicle or escalating dose of Δ9-THC through adolescence. In vehicle controls, CB1R immunolabeling was mainly localized to axonal profiles virtually devoid of M2R but often apposing M2R-immunoreactive dendrites and dendritic spines. The dendrites received inputs from CB1R-labeled or unlabeled terminals, whereas spines received asymmetric synapses exclusively from axon terminals lacking CB1Rs. Adolescent Δ9-THC significantly increased plasmalemmal M2R-immunogold density exclusively in large dendrites receiving input from CB1R-labeled terminals. In contrast, cytoplasmic M2R-immunogold density decreased in small spines of the Δ9-THC-treated adult mice. We conclude that Δ9-THC engagement of CB1Rs during adolescence increases M2R plasmalemmal accumulation in large proximal dendrites and decreases M2R cytoplasmic expression in small spines of PL-PFC.