Possible dopaminergic stimulation of locus coeruleus alpha1-adrenoceptors involved in behavioral activation.
Possible dopaminergic stimulation of locus coeruleus alpha1-adrenoceptors involved in behavioral activation.
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DOI：
10.1002/syn.20517
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发表时间：
2008-07
期刊：
影响因子：
2.3
通讯作者：
Stone, Eric A.
中科院分区：
文献类型：
--
作者：
Lin, Yan;Quartermain, David;Dunn, Adrian J.;Weinshenker, David;Stone, Eric A.
蓝斑（LC）的α1-肾上腺素能受体与新环境下的行为激活有关，但激活这些受体的内源性激动剂尚未确定。除了去甲肾上腺素（NE）对α1受体的典型激活外，有证据表明多巴胺（DA）也可以激活某些脑α1受体。本研究通过确定将各种多巴胺能和肾上腺素能药物输注到小鼠LC中的影响，检查了DA对新型笼中探索活动的贡献。结果发现，D2/D3激动剂，quinpirole，它选择性地阻止CNS DA的释放，产生了剂量依赖性和几乎完全取消的探索和所有的运动在新的笼测试。共输注DA可显着减弱昆吡罗诱导的不活动，但D1激动剂SKF 38390则不然。此外，共输注α1-肾上腺素能受体拮抗剂特拉唑嗪可阻断喹吡罗失活的DA衰减，而D1受体拮抗剂SCH 23390则不能阻断。LC输注quinpirole或terazosin也在缺乏NE的DA-β-羟化酶敲除（Dbh −/−）小鼠中产生了严重的失活，表明它们的行为效应不是由于LC NE的释放或作用的改变。在暴露于新型笼期间，LC中内源性DA、NE和5 HT及其代谢产物的测量表明DA和NE的周转增加，但5 HT未增加。这些结果表明，DA是一个候选的内源性激动剂的行为激活LC α1受体，并可能发挥作用，在激活该核的新的环境。
α1-Adrenoceptors of the locus coeruleus (LC) have been implicated in behavioral activation in novel surroundings, but the endogenous agonist that activates these receptors has not been established. In addition to the canonical activation of α1-receptors by norepinephrine (NE), there is evidence that dopamine (DA) may also activate certain brain α1-receptors. This study examined the contribution of DA to exploratory activity in a novel cage by determining the effect of infusion of various dopaminergic and adrenergic drugs into the mouse LC. It was found that the D2/D3 agonist, quinpirole, which selectively blocks the release of CNS DA, produced a dose-dependent and virtually complete abolition of exploration and all movement in the novel cage test. The quinpirole-induced inactivity was significantly attenuated by coinfusion of DA but not by the D1 agonist, SKF38390. Furthermore, the DA attenuation of quinpirole inactivity was blocked by coinfusion of the α1-adrenergic receptor antagonist, terazosin, but not by the D1 receptor antagonist, SCH23390. LC infusions of either quinpirole or terazosin also produced profound inactivity in DA-β-hydroxylase knockout (Dbh −/−) mice that lack NE, indicating that their behavioral effects were not due to an alteration of the release or action of LC NE. Measurement of endogenous DA, NE, and 5HT and their metabolites in the LC during exposure to the novel cage indicated an increase in the turnover of DA and NE but not 5HT. These results indicate that DA is a candidate as an endogenous agonist for behaviorally activating LC α1-receptors and may play a role in the activation of this nucleus by novel surroundings.
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