Corticotropin-Releasing Factor Receptors Modulate Oxytocin Release in the Dorsolateral Bed Nucleus of the Stria Terminalis (BNST) in Male Rats.
Corticotropin-Releasing Factor Receptors Modulate Oxytocin Release in the Dorsolateral Bed Nucleus of the Stria Terminalis (BNST) in Male Rats.
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DOI：
10.3389/fnins.2018.00183
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发表时间：
2018
影响因子：
4.3
通讯作者：
Dabrowska J
中科院分区：
文献类型：
--
作者：
Martinon D;Dabrowska J
神经肽催产素（OT）在社会和焦虑样行为的调节中起着重要作用。我们以前的研究表明，OT神经元从下丘脑向终纹背外侧床核（BNSTdl）发送投射，这是一个与焦虑样行为的调制密切相关的前脑区域。重要的是，BNSTdl中的这些OT末端表达突触前促肾上腺皮质激素释放因子（CRF）受体2型（CRFR 2）。这表明CRFR 2可能参与OT释放的调节。为了检验这一假设，我们测量了在施用选择性CRFR 2激动剂（Urocortin 3）或拮抗剂（Astressin 2B，As 2B）后从自由移动的雄性Sprague-Dawley大鼠的BNSTdl收集的微透析液中的OT含量。为了确定1型CRF受体（CRFR 1）是否也参与其中，我们使用了选择性CRFR 1拮抗剂（NBI 35965）以及CRFR 1和CRFR 2的推定配体CRF。所有化合物通过反向透析直接递送到BNSTdl中。采用高灵敏度、高选择性放射免疫分析法测定微透析液中OT含量。用As 2B阻断CRFR 2导致BNSTdl微透析液中OT含量增加，而Urocortin 3对CRFR 2的激活没有影响。通过应用CRFR 1拮抗剂阻断As 2B诱导的OT释放增加，表明该作用依赖于CRFR 1传输。有趣的是，CRF单独引起BNSTdl微透析液中OT含量的延迟增加，这依赖于CRF 2而不是CRF 1受体。我们的研究结果表明，CRF肽家族成员通过涉及CRFR 1和CRFR 2的微调机制调节BNSTdl中的OT释放。需要进一步探讨CRF肽家族对内源性OT系统的调节机制，以更好地理解这些神经肽在焦虑和应激反应调节中的作用。
The neuropeptide oxytocin (OT) plays an important role in the regulation of social and anxiety-like behavior. Our previous studies have shown that OT neurons send projections from the hypothalamus to the dorsolateral bed nucleus of the stria terminalis (BNSTdl), a forebrain region critically involved in the modulation of anxiety-like behavior. Importantly, these OT terminals in the BNSTdl express presynaptic corticotropin releasing factor (CRF) receptor type 2 (CRFR2). This suggests that CRFR2 might be involved in the modulation of OT release. To test this hypothesis, we measured OT content in microdialysates collected from the BNSTdl of freely-moving male Sprague-Dawley rats following the administration of a selective CRFR2 agonist (Urocortin 3) or antagonist (Astressin 2B, As2B). To determine if type 1 CRF receptors (CRFR1) are also involved, we used selective CRFR1 antagonist (NBI35965) as well as CRF, a putative ligand of both CRFR1 and CRFR2. All compounds were delivered directly into the BNSTdl via reverse dialysis. OT content in the microdialysates was measured with highly sensitive and selective radioimmunoassay. Blocking CRFR2 with As2B caused an increase in OT content in BNSTdl microdialysates, whereas CRFR2 activation by Urocortin 3 did not have an effect. The As2B-induced increase in OT release was blocked by application of the CRFR1 antagonist demonstrating that the effect was dependent on CRFR1 transmission. Interestingly, CRF alone caused a delayed increase in OT content in BNSTdl microdialysates, which was dependent on CRF2 but not CRF1 receptors. Our results suggest that members of the CRF peptide family modulate OT release in the BNSTdl via a fine-tuned mechanism that involves both CRFR1 and CRFR2. Further exploration of mechanisms by which endogenous OT system is modulated by CRF peptide family is needed to better understand the role of these neuropeptides in the regulation of anxiety and the stress response.
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影响因子：
3.2
作者：
Arima, H;Aguilera, G
通讯作者：
Aguilera, G
影响因子：
3.3
作者：
Jaferi, A.;Pickel, V. M.
通讯作者：
Pickel, V. M.
影响因子：
3.7
作者：
Bosch OJ;Dabrowska J;Modi ME;Johnson ZV;Keebaugh AC;Barrett CE;Ahern TH;Guo J;Grinevich V;Rainnie DG;Neumann ID;Young LJ
通讯作者：
Young LJ
影响因子：
3.3
作者：
Farkas, Jozsef;Kovacs, Laszlo A.;Gaszner, Balazs
通讯作者：
Gaszner, Balazs
影响因子：
4.3
作者：
Dabrowska J;Hazra R;Guo JD;Dewitt S;Rainnie DG
通讯作者：
Rainnie DG