Cocaine reward and memory after chemogenetic inhibition of distinct serotonin neuron subtypes in mice.
Cocaine reward and memory after chemogenetic inhibition of distinct serotonin neuron subtypes in mice.
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DOI：
10.1007/s00213-020-05560-6
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发表时间：
2020-09
影响因子：
3.4
通讯作者：
Kantak KM
中科院分区：
文献类型：
--
作者：
Baskin BM;Mai JJ;Dymecki SM;Kantak KM
我们通过条件位置偏好（CPP）的表达和发展，探讨了转基因小鼠血清素神经元对可卡因奖励和记忆的差异调节，这些神经元的发育基因表达为r2Hoxa2-Pet1（实验1）和Drd1a-Pet1（实验2）。为了探究在CPP中的作用，我们在体内通过使用外源性配体氯氮平- n -氧化物（CNO）激活转基因表达的合成的DREADD受体hM4Di （Di）来自主抑制神经元细胞。为了检测CPP的表达，小鼠分别使用行为活性剂量的可卡因（10.0或17.8 mg/kg）和生理盐水，然后进行CPP评估，首先没有神经元抑制（后适应阶段1），然后是cno介导的神经元抑制（后适应阶段2），然后是4个后适应阶段。为了检查CPP的发展，我们在条件反射过程中使用CNO，然后在6个条件反射后测试CPP。在r2Hoxa2-Pet1-Di小鼠中，条件反射后给药CNO不影响可卡因CPP的表达，但在条件反射期间给药CNO后，可卡因CPP （17.8 mg/kg）在整个条件反射过程中持续存在，与对照组相比，表明可卡因记忆缺失。Drd1a-Pet1-Di小鼠，在CNO- di触发神经元抑制之前，与对照组相比，意外地表达了更高的可卡因CPP(10.0和17.8 mg/kg)，并且这种基础表型被急性后适应CNO给药短暂阻断，并在适应过程中被重复CNO给药持续阻断。可卡因奖励和记忆可能与不同的血清素能Pet1神经元亚型有关。正常情况下，r2Hoxa2-Pet1神经元可能会限制可卡因记忆的持久性，但不会影响最初的可卡因奖励强度。正常情况下，Drd1a-Pet1神经元可能有助于促进可卡因奖励。
We probed serotonin neurons, those denoted by their developmental gene expression as r2Hoxa2-Pet1 (experiment 1) and Drd1a-Pet1 (experiment 2), for differential modulation of cocaine reward and memory as revealed by the expression and development of conditioned place preference (CPP) in transgenic mice. To query roles in CPP, we inhibited neurons cell autonomously in vivo by activating the transgenically expressed, synthetic DREADD receptor hM4Di (Di) with the exogenous ligand clozapine-N-oxide (CNO). To examine CPP expression, mice were conditioned using behaviorally active doses of cocaine (10.0 or 17.8 mg/kg) vs. saline followed by CPP assessment, first without neuron inhibition (post-conditioning session 1), and then with CNO-mediated neuron inhibition (post-conditioning session 2), followed by 4 more post-conditioning sessions. To examine CPP development, we administered CNO during conditioning sessions and then assayed CPP across 6 post-conditioning sessions. In r2Hoxa2-Pet1-Di mice, post-conditioning CNO administration did not impact cocaine CPP expression, but after CNO administration during conditioning, cocaine CPP (17.8 mg/kg) persisted across post-conditioning sessions compared with that in controls, suggesting a deficit in extinguishing cocaine memory. Drd1a-Pet1-Di mice, prior to CNO-Di-triggered neuronal inhibition, unexpectedly expressed heightened cocaine CPP (10.0 and 17.8 mg/kg) compared with controls, and this basal phenotype was transiently blocked by acute post-conditioning CNO administration and persistently blocked by repeated CNO administration during conditioning. Cocaine reward and memory likely map to distinct serotonergic Pet1 neuron subtypes. r2Hoxa2-Pet1 neurons normally may limit the durability of cocaine memory, without impacting initial cocaine reward magnitude. Drd1a-Pet1 neurons normally may help to promote cocaine reward.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
8.2
作者：
George, Olivier;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
1.7
作者：
Bernardi RE;Lattal KM
通讯作者：
Lattal KM
影响因子：
25
作者：
Bock, Roland;Shin, J. Hoon;Kaplan, Alanna R.;Dobi, Alice;Markey, Eric;Kramer, Paul F.;Gremel, Christina M.;Christensen, Christine H.;Adrover, Martin F.;Alvarez, Veronica A.
通讯作者：
Alvarez, Veronica A.
DOI：
10.1111/j.1460-9568.2011.07936.x
发表时间：
2012-01
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Bang SJ;Jensen P;Dymecki SM;Commons KG
通讯作者：
Commons KG