Orexinergic modulation of serotonin neurons in the dorsal raphe of a diurnal rodent, Arvicanthis niloticus
Orexinergic modulation of serotonin neurons in the dorsal raphe of a diurnal rodent, Arvicanthis niloticus
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DOI：
10.1016/j.yhbeh.2019.104584
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发表时间：
2019-11-01
影响因子：
3.5
通讯作者：
Yan, Lily
中科院分区：
文献类型：
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作者：
Adidharma, Widya;Deats, Sean P.;Yan, Lily
下丘脑神经肽，食欲素(或下丘脑)，与许多生理和行为功能有关，包括情绪状态，如抑郁和焦虑。食欲素调节情感反应的潜在机制和神经回路仍不清楚。本研究的目的是验证一种假设，即中缝背核(DRN)的5-羟色胺(5-HT)系统是食欲素潜在地在情感状态中发挥作用的下游靶点。以一只昼夜活动的尼罗河鼠(Arvicanthis Niloticus)为研究对象，我们首次用原位杂交的方法研究了增食欲素受体OX1R和OX2R在DRN中的表达。结果显示，OX1R和OX2R的mRNAs分布不同，其中OX1R主要表达在参与情感过程的DRN的背翼和外侧翼，而OX2R主要表达在与感觉运动功能密切相关的腹侧DRN。接下来，我们使用选择性氧合酶1R拮抗剂SB-334867(10 mg/kg，i.p.)研究了增食欲素-氧合酶1受体通路如何调节背根神经节及其部分投射部位的5-羟色胺。单次注射SB-334867可减少扣带回前皮质内的5-羟色胺免疫反应阳性纤维，每天给药5次的SB-334867不仅可减少扣带回前皮质内的5-羟色胺免疫反应阳性纤维，还可减少延髓背根核、终纹椭圆形床核、伏隔核壳核和中脑导水管周围灰质中的5-羟色胺免疫反应。高效液相分析显示，每天给药五次SB-334867并不影响5-羟色胺在这五个部位中的任何一个的周转，尽管它增加了NAcsh中5-羟色胺和5-HIAA的水平。这些结果提示，食欲素通过OX1Rs对DRN 5-羟色胺能神经元的调节可能是食欲素调节情绪和焦虑的途径之一，可能还有其他神经生物学过程。
The hypothalamic neuropeptide, orexin (or hypocretin), is implicated in numerous physiology and behavioral functions, including affective states such as depression and anxiety. The underlying mechanisms and neural circuits through which orexin modulates affective responses remain unclear. The objective of the present study was to test the hypothesis that the serotonin (5-HT) system of the dorsal raphe nucleus (DRN) is a downstream target through which orexin potentially manifests its role in affective states. Using a diurnal rodent, the Nile grass rat (Arvicanthis niloticus), we first characterized the expression of the orexin receptors OX1R and OX2R in the DRN using in situ hybridization. The results revealed distinct distributions of OX1R and OX2R mRNAs, with OX1R predominantly expressed in the dorsal and lateral wings of the DRN that are involved in affective processes, while OX2R was mostly found in the ventral DRN that is more involved in sensory-motor function. We next examined how the orexin-OX1R pathway regulates 5-HT in the DRN and some of its projection sites using a selective OX1R antagonist SB-334867 (10 mg/kg, i.p.). A single injection of SB-334867 decreased 5-HT-ir fibers within the anterior cingulate cortex (aCgC); five once-daily administrations of SB-334867 decreased 5-HT-ir not only in the aCgC but also in the DRN, oval bed nucleus of the stria terminalis (ovBNST), nucleus accumbens shell (NAcSh), and periaqueductal gray (PAG). HPLC analysis revealed that five once-daily administrations of SB-334867 did not affect 5-HT turnover to any of the five sites, although it increased the levels of both 5-HT and 5-HIAA in the NAcSh. These results together suggest that orexinergic modulation of DRN 5-HT neurons via OX1Rs may be one pathway through which orexin regulates mood and anxiety, as well as perhaps other neurobiological processes.