Corticotropin-releasing factor in the dorsal raphe nucleus increases medial prefrontal cortical serotonin via type 2 receptors and median raphe nucleus activity
Corticotropin-releasing factor in the dorsal raphe nucleus increases medial prefrontal cortical serotonin via type 2 receptors and median raphe nucleus activity
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DOI：
10.1111/j.1460-9568.2008.06333.x
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发表时间：
2008-07-01
影响因子：
3.4
通讯作者：
Renner, Kenneth J.
中科院分区：
文献类型：
--
作者：
Forster, Gina L.;Pringle, Ronald B.;Renner, Kenneth J.
中枢促肾上腺皮质激素释放因子（CRF）和血清素能系统之间的相互作用被认为是介导恐惧和焦虑行为的重要因素。最近，我们证明将CRF注入大鼠中缝背核会导致内侧前额叶皮层内血清素释放的延迟增加，这与恐惧行为的减少相一致。目前的研究旨在研究CRF受体机制和参与这种血清素能反应的途径。用muscimol （25 ng/0.25 μ L）使中缝正中核失活，用antalarmin （25-50 ng/0.5 μ L）或anti - sauvagin -30 （2 mu g/0.5 μ L）拮抗中缝背核CRF 1型或CRF 2型受体，分别向氨基乙酯麻醉大鼠中缝背核输注CRF （0.5 μ g/0.5 μ L）。采用体内微透析和高效液相色谱电化学检测检测内侧前额叶皮层血清素水平。中缝正中核失活可消除中缝背核灌注CRF引起的内侧前额叶皮层血清素释放增加。此外，中缝背核中CRF受体2型的拮抗作用，而不是CRF受体1型的拮抗作用，可以消除CRF诱导的内侧前额叶皮层血清素的增加。后续研究包括对杏仁核的中央核进行电刺激，杏仁核是中缝背核的CRF传入源。中央核的激活增加了内侧前额叶皮层血清素的释放。这种反应在背缝中被CRF受体2型拮抗剂阻断。总的来说，这些结果突出了复杂的CRF调节内侧前额叶皮层在中缝核水平上的血清素能活性。
Interactions between central corticotropin-releasing factor (CRF) and serotonergic systems are believed to be important for mediating fear and anxiety behaviors. Recently we demonstrated that infusions of CRF into the rat dorsal raphe nucleus result in a delayed increase in serotonin release within the medial prefrontal cortex that coincided with a reduction in fear behavior. The current studies were designed to study the CRF receptor mechanisms and pathways involved in this serotonergic response. Infusions of CRF (0.5 mu g/0.5 mu L) were made into the dorsal raphe nucleus of urethane-anesthetized rats following either inactivation of the median raphe nucleus by muscimol (25 ng/0.25 mu L) or antagonism of CRF receptor type 1 or CRF receptor type 2 in the dorsal raphe nucleus with antalarmin (25-50 ng/0.5 mu L) or antisauvagine-30 (2 mu g/0.5 mu L), respectively. Medial prefrontal cortex serotonin levels were measured using in-vivo microdialysis and high-performance liquid chromatography with electrochemical detection. Increased medial prefrontal cortex serotonin release elicited by CRF infusion into the dorsal raphe nucleus was abolished by inactivation of the median raphe nucleus. Furthermore, antagonism of CRF receptor type 2 but not CRF receptor type 1 in the dorsal raphe nucleus abolished CRF-induced increases in medial prefrontal cortex serotonin. Follow-up studies involved electrical stimulation of the central nucleus of the amygdala, a source of CRF afferents to the dorsal raphe nucleus. Activation of the central nucleus increased medial prefrontal cortex serotonin release. This response was blocked by CRF receptor type 2 antagonism in the dorsal raphe. Overall, these results highlight complex CRF modulation of medial prefrontal cortex serotonergic activity at the level of the raphe nuclei.