Carneiro-Nascimento Simone, Powell William, Uebel Michaela, Buerge Michaela, Sigrist Hannes, Patterson Michael, Pryce Christopher R, Opacka-Juffry Jolanta
Department of Life Sciences, University of Roehampton, London SW15 4JD, UK.
Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy & Psychosomatics, University of Zurich, Zurich, Switzerland.
IBRO Neurosci Rep. 2021 Feb 3;10:8-16. doi: 10.1016/j.ibneur.2020.11.001. eCollection 2021 Jun.
Serotonin (5-HT), via its receptors expressed in discrete brain regions, modulates aversion and reward processing and is implicated in various psychiatric disorders including depression. Stressful experiences affect central serotonergic activity and act as a risk factor for depression; this can be modelled preclinically. In adult male C57BL/6J mice, 15-day chronic social stress (CSS) leads to depression-relevant behavioural states, including increased aversion and reduced reward sensitivity. Based on this evidence, here we investigated CSS effects on 5-HT1A, 5-HT2A, and 5-HT2C receptor binding in discrete brain regions using in vitro quantitative autoradiography with selective radioligands. In addition, mRNA expression of and (5-HT transporter) was measured by quantitative PCR. Relative to controls, the following effects were observed in CSS mice: 5-HT1A receptor binding was markedly increased in the dorsal raphe nucleus (136%); mRNA expression was increased in raphe nuclei (19%), medial prefrontal cortex (35%), and hypothalamic para- and periventricular nuclei (21%) and ventral medial nucleus (38%). 5-HT2A receptor binding was decreased in the amygdala (48%) and ventral tegmental area (60%); mRNA expression was increased in the baso-lateral amygdala (116%). 5-HT2C receptor binding was decreased in the dorsal raphe nucleus (42%). mRNA expression was increased in the raphe (59%). The present findings add to the translational evidence that chronic social stress impacts on the central serotonergic system in a region- and receptor-specific manner, and that this altered state of the serotonergic system contributes to stress-induced dysfunctions in emotional processing.
血清素（5-羟色胺，5-HT）通过其在离散脑区表达的受体，调节厌恶和奖赏处理，并与包括抑郁症在内的各种精神疾病有关。应激经历会影响中枢5-羟色胺能活性，并作为抑郁症的一个风险因素；这在临床前可以进行模拟。在成年雄性C57BL/6J小鼠中，15天的慢性社会应激（CSS）会导致与抑郁相关的行为状态，包括厌恶增加和奖赏敏感性降低。基于这一证据，我们在此使用选择性放射性配体的体外定量放射自显影技术，研究了CSS对离散脑区5-HT1A、5-HT2A和5-HT2C受体结合的影响。此外，通过定量PCR测量了5-HT转运体（5-HTT）的mRNA表达。与对照组相比，在CSS小鼠中观察到以下效应：中缝背核中5-HT1A受体结合显著增加（136%）；5-HTT mRNA表达在中缝核（19%）、内侧前额叶皮质（35%）、下丘脑室旁核和室周核（21%）以及腹内侧核（38%）中增加。杏仁核（48%）和腹侧被盖区（60%）中5-HT2A受体结合减少；基底外侧杏仁核中5-HTT mRNA表达增加（116%）。中缝背核中5-HT2C受体结合减少（42%）。中缝中5-HTT mRNA表达增加（59%）。本研究结果进一步补充了转化证据，即慢性社会应激以区域和受体特异性方式影响中枢5-羟色胺能系统，并且这种5-羟色胺能系统的改变状态导致了应激诱导的情绪加工功能障碍。
