Cooper M A, Grober M S, Nicholas C R, Huhman K L
Department of Psychology, University of Tennessee, Knoxville, TN 37996-0900, USA.
Neuroscience. 2009 Jul 7;161(3):680-90. doi: 10.1016/j.neuroscience.2009.03.084. Epub 2009 Apr 9.
Serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN) have been implicated in stress-induced changes in behavior. Previous research indicates that stressful stimuli activate 5-HT neurons in select subregions of the DRN. Uncontrollable stress is thought to sensitize 5-HT neurons in the DRN and allow for an exaggerated 5-HT response to future stimuli. In the current study, we tested the hypothesis that following aggressive encounters, losing male Syrian hamsters would exhibit increased c-Fos immunoreactivity in 5-HT DRN neurons compared to winners or controls. In addition, we tested the hypothesis that losers would have decreased 5-HT1A mRNA levels in the DRN compared to winners or controls. We found that a single 15-min aggressive encounter increased c-Fos expression in 5-HT and non-5-HT neurons in losers compared to winners and controls. The increased c-Fos expression in losers was restricted to ventral regions of the rostral DRN. We also found that four 5-min aggressive encounters reduced total 5-HT1A mRNA levels in the DRN in losers compared to winners and controls, and that differences in mRNA levels were not restricted to specific DRN subregions. These results suggest that social defeat activates neurons in select subregions of the DRN and reduces message for DRN 5-HT1A autoreceptors. Our results support the hypothesis that social stress can activate 5-HT neurons in the DRN, reduce 5-HT1A autoreceptor-mediated inhibition, and lead to hyperactivity of 5-HT neurons.
中缝背核（DRN）中的5-羟色胺能（5-HT）神经元与应激诱导的行为变化有关。先前的研究表明，应激刺激会激活DRN特定子区域中的5-HT神经元。不可控应激被认为会使DRN中的5-HT神经元敏感化，并使5-HT对未来刺激产生过度反应。在当前的研究中，我们测试了以下假设：在攻击性遭遇后，与获胜者或对照组相比，失败的雄性叙利亚仓鼠在5-HT DRN神经元中的c-Fos免疫反应性会增加。此外，我们测试了另一个假设：与获胜者或对照组相比，失败者DRN中的5-HT1A mRNA水平会降低。我们发现，与获胜者和对照组相比，单次15分钟的攻击性遭遇会增加失败者中5-HT和非5-HT神经元中的c-Fos表达。失败者中c-Fos表达的增加仅限于吻侧DRN的腹侧区域。我们还发现，与获胜者和对照组相比，四次5分钟的攻击性遭遇会降低失败者DRN中的总5-HT1A mRNA水平，并且mRNA水平的差异并不局限于特定的DRN子区域。这些结果表明，社会挫败会激活DRN特定子区域中的神经元，并减少DRN 5-HT1A自身受体的信息。我们的结果支持以下假设：社会应激可激活DRN中的5-HT神经元，减少5-HT1A自身受体介导的抑制作用，并导致5-HT神经元的活动亢进。
