Reelin deficiency exacerbates cocaine-induced hyperlocomotion by enhancing neuronal activity in the dorsomedial striatum.
Reelin deficiency exacerbates cocaine-induced hyperlocomotion by enhancing neuronal activity in the dorsomedial striatum.
复制标题
DOI：
10.1111/gbb.12828
复制
发表时间：
2022-09
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
Reln基因编码细胞外糖蛋白Reelin，其调节从发育到成年的几种脑功能，包括神经元迁移、树突生长和分支以及突触形成和可塑性。人类研究表明，Reelin信号传导与几种神经发育和精神疾病有关。使用杂合Reeler（HR）小鼠的小鼠研究表明，Reln表达水平降低与学习和记忆缺陷以及抑制解除增加相关。虽然这些特征与物质使用障碍有关，但Reelin在成瘾药物的细胞和行为反应中的作用在很大程度上仍然未知。在这里，我们将HR小鼠与野生型（WT）同窝对照小鼠进行了比较，以研究Reelin信号传导是否有助于可卡因的过度运动和奖励作用。在单次或重复注射可卡因后，与WT对照组相比，HR小鼠显示出可卡因诱导的自发活动增强。这种影响在停药后持续存在。相比之下，Reelin缺乏不会诱导可卡因致敏，也不会影响条件性位置偏好试验中测量的可卡因的奖励作用。与WT相比，HR小鼠中可卡因诱导的过度运动增加与背内侧纹状体（DMS）中Fos蛋白表达增加相关。最后，我们进行了RNA荧光原位杂交实验，发现Reln与DMS中编码多巴胺受体D1的Drd1基因高度共表达。这些发现表明，Reelin信号有助于可卡因的运动效应，并提高了我们对可卡因的细胞和行为效应的神经生物学机制的理解。杂合子Reeler（HR）小鼠中的Reelin缺乏增强了可卡因诱导的运动活动，但没有可卡因的奖励作用。与WT相比，HR小鼠中可卡因诱导的过度运动增加与背内侧纹状体（DMS）中Fos蛋白表达增加相关。
The Reln gene encodes for the extracellular glycoprotein Reelin, which regulates several brain functions from development to adulthood, including neuronal migration, dendritic growth and branching and synapse formation and plasticity. Human studies have implicated Reelin signaling in several neurodevelopmental and psychiatric disorders. Mouse studies using the heterozygous Reeler (HR) mice have shown that reduced levels of Reln expression are associated with deficits in learning and memory and increased disinhibition. Although these traits are relevant to substance use disorders, the role of Reelin in cellular and behavioral responses to addictive drugs remains largely unknown. Here, we compared HR mice to wild‐type (WT) littermate controls to investigate whether Reelin signaling contributes to the hyperlocomotor and rewarding effects of cocaine. After a single or repeated cocaine injections, HR mice showed enhanced cocaine‐induced locomotor activity compared with WT controls. This effect persisted after withdrawal. In contrast, Reelin deficiency did not induce cocaine sensitization, and did not affect the rewarding effects of cocaine measured in the conditioned place preference assay. The elevated cocaine‐induced hyperlocomotion in HR mice was associated with increased protein Fos expression in the dorsal medial striatum (DMS) compared with WT. Lastly, we performed an RNA fluorescent in situ hybridization experiment and found that Reln was highly co‐expressed with the Drd1 gene, which encodes for the dopamine receptor D1, in the DMS. These findings show that Reelin signaling contributes to the locomotor effects of cocaine and improve our understanding of the neurobiological mechanisms underlying the cellular and behavioral effects of cocaine. Reelin deficiency in the heterozygous Reeler (HR) mice enhances cocaine‐induced locomotor activity but not the rewarding effects of cocaine. The elevated cocaine‐induced hyper‐locomotion in HR mice was associated with increased protein Fos expression in the dorsal medial striatum (DMS) compared with WT.
登录
查看更多内容
影响因子：
2.9
作者：
Ognibene, Elisa;Adriani, Walter;Laviola, Giovanni
通讯作者：
Laviola, Giovanni
影响因子：
16.6
作者：
Bariselli, Sebastiano;Miyazaki, Nanami L.;Kravitz, Alexxai, V
通讯作者：
Kravitz, Alexxai, V
影响因子：
2.1
作者：
Borbelyova, V;Janisova, K.;Riljak, V
通讯作者：
Riljak, V
影响因子：
4.7
作者：
Folsom TD;Fatemi SH
通讯作者：
Fatemi SH
影响因子：
16.2
作者：
Hiesberger, T;Trommsdorff, M;Herz, J
通讯作者：
Herz, J