Lopes Danielle A, Lemes Jéssica A, Melo-Thomas Liana, Schor Herbert, de Andrade José S, Machado Carla M, Horta-Júnior José A C, Céspedes Isabel C, Viana Milena B
Department of Biosciences, Federal University of São Paulo (UNIFESP), Santos, SP, Brazil.
Behavioral Neuroscience, Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg, Germany.
Behav Brain Res. 2016 Jan 15;297:180-6. doi: 10.1016/j.bbr.2015.10.006. Epub 2015 Oct 20.
In previous studies, we verified that exposure to unpredictable chronic mild stress (UCMS) facilitates avoidance responses in the elevated T-maze (ETM) and increased Fos-immunoreactivity in different brain structures involved in the regulation of anxiety, including the dorsal raphe (DR). Since, it has been shown that the DR is composed of distinct subpopulations of serotonergic and non-serotonergic neurons, the present study investigated the pattern of activation of these different subnuclei of the region in response to this stress protocol. Male Wistar rats were either unstressed or exposed to the UCMS procedure for two weeks and, subsequently, analyzed for Fos-immunoreactivity (Fos-ir) in serotonergic cells of the DR. To verify if the anxiogenic effects observed in the ETM could be generalized to other anxiety models, a group of animals was also tested in the light/dark transition test after UCMS exposure. Results showed that the UCMS procedure decreased the number of transitions and increased the number of stretched attend postures in the model, an anxiogenic effect. UCMS exposure also increased Fos-ir and the number of double-labeled neurons in the mid-rostral subdivision of the dorsal part of the DR and in the mid-caudal region of the lateral wings. In the caudal region of the DR there was a significant increase in the number of Fos-ir. No significant effects were found in the other DR subnuclei. These results corroborate the idea that neurons of specific subnuclei of the DR regulate anxiety responses and are differently activated by chronic stress exposure.
在先前的研究中,我们证实,暴露于不可预测的慢性轻度应激(UCMS)会促进高架T迷宫(ETM)中的回避反应,并增加参与焦虑调节的不同脑结构(包括中缝背核(DR))中的Fos免疫反应性。由于已经表明DR由血清素能和非血清素能神经元的不同亚群组成,因此本研究调查了该区域这些不同亚核在应对这种应激方案时的激活模式。将雄性Wistar大鼠分为未受应激组或暴露于UCMS程序两周,随后分析DR血清素能细胞中的Fos免疫反应性(Fos-ir)。为了验证在ETM中观察到的致焦虑作用是否可以推广到其他焦虑模型,一组动物在暴露于UCMS后还进行了明暗转换测试。结果表明,UCMS程序减少了模型中的转换次数,并增加了伸展姿势的次数,这是一种致焦虑作用。暴露于UCMS还增加了DR背侧部中 Rostral 亚区和侧翼中尾区的Fos-ir和双标记神经元的数量。在DR的尾侧区域,Fos-ir的数量显著增加。在其他DR亚核中未发现显著影响。这些结果证实了DR特定亚核的神经元调节焦虑反应并在慢性应激暴露下被不同激活的观点。