Dopamine-induced plasticity, phospholipase D (PLD) activity and cocaine-cue behavior depend on PLD-linked metabotropic glutamate receptors in amygdala.
Dopamine-induced plasticity, phospholipase D (PLD) activity and cocaine-cue behavior depend on PLD-linked metabotropic glutamate receptors in amygdala.
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DOI：
10.1371/journal.pone.0025639
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Shinnick-Gallagher P
中科院分区：
文献类型：
--
作者：
Krishnan B;Genzer KM;Pollandt SW;Liu J;Gallagher JP;Shinnick-Gallagher P
可卡因-线索关联会诱导突触可塑性，并导致杏仁核中持久的分子和细胞变化，而杏仁核是线索相关记忆机制的关键部位。潜在的神经适应可能包括通过多巴胺 (DA) 受体 (DR) 和代谢型谷氨酸 (Glu) 受体 (mGluR) 信号传导的显着改变。此前，我们报道了 DR 拮抗剂阻断了重复给予可卡因的 Sprague-Dawley 大鼠杏仁核切片的突触可塑性。在本研究中，我们研究了外源 DA 诱导的突触可塑性及其对 mGluR 信号传导的依赖性，以及磷脂酶 D (PLD) 作为与 mGluR 和 DR 信号传导相关的下游元件的潜在作用。利用改良的条件性位置偏好（CPP）范式作为功能性行为测量，我们研究了最后一次可卡因条件反射两周后的神经生理学影响。我们从电生理学角度记录了 DR 诱导的基底外侧到外侧囊中央杏仁核 (BLA-lcCeA) 突触通路的突触增强，该通路被 I 组 mGluR 拮抗剂（特别是 PLD 连接的 mGluR）阻断。此外，我们观察到 PLD 表达增加了 2-2.5 倍，基础 PLD 酶活性增加了 3.7 倍。 DA D1 样 (D1/5R) 受体激动剂可进一步刺激增强的 PLD 活性（9.3 倍），而 mGluR1 和 PLD 连接的 mGluR 拮抗剂可将其降低至对照水平。在测试前 15 分钟，即最后一次可卡因注射两周后，通过在杏仁核中输注 PLD 连接的 mGluR 拮抗剂 PCCG-13，观察到 CPP 减少。这些结果意味着 D1/5R、I 组 mGluR 之间通过 PLD 在与可卡因提示相关的杏仁核突触可塑性中存在功能性相互作用。
Cocaine-cue associations induce synaptic plasticity with long lasting molecular and cellular changes in the amygdala, a site crucial for cue-associated memory mechanisms. The underlying neuroadaptations can include marked alterations in signaling via dopamine (DA) receptors (DRs) and metabotropic glutamate (Glu) receptors (mGluRs). Previously, we reported that DR antagonists blocked forms of synaptic plasticity in amygdala slices of Sprague-Dawley rats withdrawn from repeated cocaine administration. In the present study, we investigated synaptic plasticity induced by exogenous DA and its dependence on mGluR signaling and a potential role for phospholipase D (PLD) as a downstream element linked to mGluR and DR signaling. Utilizing a modified conditioned place preference (CPP) paradigm as a functional behavioral measure, we studied the neurophysiological effects after two-weeks to the last cocaine conditioning. We recorded, electrophysiologically, a DR-induced synaptic potentiation in the basolateral to lateral capsula central amygdala (BLA-lcCeA) synaptic pathway that was blocked by antagonists of group I mGluRs, particularly, the PLD-linked mGluR. In addition, we observed 2–2.5 fold increase in PLD expression and 3.7-fold increase in basal PLD enzyme activity. The enhanced PLD activity could be further stimulated (9.3 fold) by a DA D1-like (D1/5R) receptor agonist, and decreased to control levels by mGluR1 and PLD-linked mGluR antagonists. Diminished CPP was observed by infusion of a PLD-linked mGluR antagonist, PCCG-13, in the amygdala 15 minutes prior to testing, two weeks after the last cocaine injection. These results imply a functional interaction between D1/5Rs, group I mGluRs via PLD in the amygdala synaptic plasticity associated with cocaine-cues.
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影响因子：
5.3
作者：
CAMPEAU, S;DAVIS, M
通讯作者：
DAVIS, M
影响因子：
25
作者：
Bissière, S;Humeau, Y;Lüthi, A
通讯作者：
Lüthi, A
影响因子：
3.3
作者：
Du, GW;Huang, P;Frohman, MA
通讯作者：
Frohman, MA
影响因子：
7.6
作者：
Bäckström, P;Hyytiä, P
通讯作者：
Hyytiä, P
DOI：
10.1073/pnas.98.4.1976
发表时间：
2001-02-13
影响因子：
11.1
作者：
Ciccocioppo, R;Sanna, PP;Weiss, F
通讯作者：
Weiss, F