Wscieklica Tatiana, Silva Mariana S C F, Lemes Jéssica A, Melo-Thomas Liana, Céspedes Isabel C, Viana Milena B
Departamento de Biociências, Universidade Federal de São Paulo, 11060-001, Santos, Brazil.
Behavioral Neuroscience, Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg, Germany.
Behav Brain Res. 2017 Mar 15;321:193-200. doi: 10.1016/j.bbr.2016.11.054. Epub 2016 Dec 27.
One of the main neurochemical systems associated with anxiety/panic is the serotonergic system originating from the dorsal raphe nucleus (DR). Previous evidence suggests that the DR is composed of distinct subpopulations of neurons, both morphologically and functionally distinct. It seems that mainly the dorsal region of the DR (DRD) regulates anxiety-related reactions, while lateral wings DR (lwDR) serotonin (5-HT) neurons inhibit panic-related responses. In this study we used the technique of deep brain stimulation (DBS) to investigate the role played by the DRD and lwDR in defense. Male Wistar rats were submitted to high-frequency stimulation (100μA, 100Hz) in one of the two DR regions for 1h and immediately after tested in the avoidance or escape tasks of the elevated T-maze (ETM). In clinical terms, these responses have been related to generalized anxiety and panic disorder, respectively. After being submitted to the ETM, animals were placed in an open field for locomotor activity assessment. An additional group of rats was submitted to DBS of the DRD or the lwDR and used for quantification of c-Fos immunoreactive (Fos-ir) neurons in brain regions related to the modulation of defense. Results showed that stimulation of the DRD decreased avoidance latencies, an anxiolytic-like effect. DRD stimulation also led to increases in Fos-ir in the medial amygdala, lateral septum and cingulate cortex. DBS applied to the lwDR increased escape latencies, a panicolytic-like effect. This data highlights the importance of raphe topography and the potential benefit of the DBS technique for the treatment of anxiety-related disorders.
与焦虑/惊恐相关的主要神经化学系统之一是起源于中缝背核（DR）的血清素能系统。先前的证据表明，中缝背核由形态和功能均不同的神经元亚群组成。似乎主要是中缝背核的背侧区域（DRD）调节与焦虑相关的反应，而中缝背核侧翼（lwDR）的血清素（5-HT）神经元抑制与惊恐相关的反应。在本研究中，我们使用深部脑刺激（DBS）技术来研究DRD和lwDR在防御中所起的作用。将雄性Wistar大鼠的两个DR区域之一进行高频刺激（100μA，100Hz），持续1小时，并在刺激后立即在高架T迷宫（ETM）的回避或逃避任务中进行测试。从临床角度来看，这些反应分别与广泛性焦虑和惊恐障碍有关。在进行ETM测试后，将动物置于旷场中以评估其运动活动。另一组大鼠接受DRD或lwDR的DBS，并用于量化与防御调节相关的脑区中c-Fos免疫反应性（Fos-ir）神经元。结果表明，刺激DRD可缩短回避潜伏期，具有类似抗焦虑的作用。刺激DRD还导致杏仁核内侧、外侧隔区和扣带回皮质中Fos-ir增加。对lwDR进行DBS可延长逃避潜伏期，具有类似抗惊恐的作用。这些数据突出了中缝核拓扑结构的重要性以及DBS技术在治疗焦虑相关疾病方面的潜在益处。
