Dopamine D2 receptor desensitization by dopamine or corticotropin releasing factor in ventral tegmental area neurons is associated with increased glutamate release.
Dopamine D2 receptor desensitization by dopamine or corticotropin releasing factor in ventral tegmental area neurons is associated with increased glutamate release.
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DOI：
10.1016/j.neuropharm.2014.03.006
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发表时间：
2014-07
影响因子：
4.7
通讯作者：
Brodie MS
中科院分区：
文献类型：
--
作者：
Nimitvilai S;Herman M;You C;Arora DS;McElvain MA;Roberto M;Brodie MS
腹侧被盖区（VTA）的神经元是多巴胺能（DA能）输入到与成瘾相关的重要脑区的来源。这些腹侧被盖区神经元长时间暴露于中等浓度的多巴胺（DA）会导致DA诱导的抑制的时间依赖性降低，这是一种称为DA抑制逆转（DA inhibition reversal，DA inhibition reversal）的复杂脱敏。D2和D1样DA受体的同时刺激，或D2刺激与某些Gq相关受体的激活同时进行，可通过常规蛋白激酶C（cPKC）介导D2和D1样DA受体的激活。促肾上腺皮质激素释放因子（CRF）通过Gq发挥作用，并可调节腹侧被盖区的多巴胺能神经传递。在本研究中，我们使用脑切片电生理学来表征DA、谷氨酸拮抗剂和CRF激动剂在腹侧被盖区中诱导和维持多巴胺的相互作用。谷氨酸受体拮抗剂阻断诱导，但不维持的ESTA。神经递质释放和钙库操纵的钙通道的假定阻断剂阻断和逆转了钙通道。CRF和CRF激动剂urocortin逆转了D2激动剂quinpirole产生的抑制，这与我们早期的工作一致，表明Gq激活逆转了quinpirole介导的抑制。在全细胞记录中，尿皮质素和quinpirole的组合，但不是任何一个单独的代理，增加自发兴奋性突触后电流（sEPSC）在腹侧被盖区神经元。同样，D1样受体激动剂和喹吡罗的组合，但不是单独的任何一种药物，增加VTA神经元中的sEPSC。总之，多巴胺或CRF诱导的DA能腹侧被盖区神经元上D2受体的脱敏与腹侧被盖区谷氨酸能信号传导的增加有关。
Neurons of the ventral tegmental area (VTA) are the source of dopaminergic (DAergic) input to important brain regions related to addiction. Prolonged exposure of these VTA neurons to moderate concentrations of dopamine (DA) causes a time-dependent decrease in DA-induced inhibition, a complex desensitization called DA inhibition reversal (DIR). DIR is mediated by conventional protein kinase C (cPKC) through concurrent stimulation of D2 and D1-like DA receptors, or by D2 stimulation concurrent with activation of some Gq-linked receptors. Corticotropin releasing factor (CRF) acts via Gq, and can modulate glutamatergic neurotransmission in the VTA. In the present study, we used brain slice electrophysiology to characterize the interaction of DA, glutamate antagonists, and CRF agonists in the induction and maintenance of DIR in the VTA. Glutamate receptor antagonists blocked induction but not maintenance of DIR. Putative blockers of neurotransmitter release and store-operated calcium channels blocked and reversed DIR. CRF and the CRF agonist urocortin reversed inhibition produced by the D2 agonist quinpirole, consistent with our earlier work indicating that Gq activation reverses quinpirole-mediated inhibition. In whole cell recordings, the combination of urocortin and quinpirole, but not either agent alone, increased spontaneous excitatory postsynaptic currents (sEPSCs) in VTA neurons. Likewise, the combination of a D1-like receptor agonist and quinpirole, but not either agent alone, increased sEPSCs in VTA neurons. In summary, desensitization of D2 receptors induced by dopamine or CRF on DAergic VTA neurons is associated with increased glutamatergic signaling in the VTA.
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DOI：
10.1523/jneurosci.1393-11.2011
发表时间：
2011-08-03
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Blacktop JM;Seubert C;Baker DA;Ferda N;Lee G;Graf EN;Mantsch JR
通讯作者：
Mantsch JR
影响因子：
3.4
作者：
Andre, Veronique M.;Cepeda, Carlos;Levine, Michael S.
通讯作者：
Levine, Michael S.
影响因子：
5.3
作者：
Carr, DB;Sesack, SR
通讯作者：
Sesack, SR
影响因子：
7.6
作者：
Gurevich, EV;Joyce, JN
通讯作者：
Joyce, JN
影响因子：
2.9
作者：
BRODIE, MS;SHEFNER, SA;DUNWIDDIE, TV
通讯作者：
DUNWIDDIE, TV