Calfa Gastón, Bussolino Daniela, Molina Victor A
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, 5000 Córdoba, Argentina.
Behav Brain Res. 2007 Jul 19;181(1):23-34. doi: 10.1016/j.bbr.2007.03.020. Epub 2007 Mar 19.
An important area of the brain aversive circuitry is the lateral septum (LS), together with its principal connections to diverse Hippocampal regions. The aim of this work was to evaluate whether the LS-Hippocampus network participates in the increased anxiety-like behavior produced by a previous defeat experience. The neural activation of different regions of the Hippocampus was assessed by the number of Fos positive cells in animals previously defeated. A notable elevation in the expression of this protein was observed in CA1, CA2, CA3, and Dentate Gyrus, for both dorsal and ventral Hippocampus. The local administration of a glucocorticoid receptor (GR or type II) antagonist, but not of a mineralcorticoid receptor (MR or type II) antagonist, into the LS before the stressful stimuli prevented a rise in the number of Fos positive cells, especially in the ventral portion of the Hippocampus. Furthermore, to evaluate the role of these hippocampal portions in the modulation of the emotional sequelae induced by defeat, the dorsal or the ventral Hippocampus were inactivated by lidocaine at different times following the social confrontation, with the anxiety-like behavior being assessed in the elevated plus maze the next day. Only the inactivation of the ventral region attenuated the excessive anxiety exhibited by defeated animals. The infusion of lidocaine, 1h after the confrontation, did not affect this behavioral response. These data suggest a preferential participation of the LS and its connections to the ventral Hippocampus in the emotional sequelae induced by the social defeat. Moreover, the GR localized within the LS played an essential role in the modulation of this emotional state.
大脑厌恶回路的一个重要区域是外侧隔核（LS），以及它与不同海马区域的主要连接。这项工作的目的是评估LS-海马网络是否参与了先前失败经历所产生的焦虑样行为增加。通过先前失败动物中Fos阳性细胞的数量来评估海马不同区域的神经激活情况。在背侧和腹侧海马的CA1、CA2、CA3和齿状回中均观察到该蛋白表达显著升高。在应激刺激前，向LS局部注射糖皮质激素受体（GR或II型）拮抗剂，而非盐皮质激素受体（MR或I型）拮抗剂，可防止Fos阳性细胞数量增加，尤其是在海马腹侧部分。此外，为了评估这些海马部分在调节失败诱导的情绪后遗症中的作用，在社交对抗后的不同时间，用利多卡因使背侧或腹侧海马失活，第二天在高架十字迷宫中评估焦虑样行为。只有腹侧区域失活可减轻失败动物表现出的过度焦虑。在对抗后1小时注射利多卡因，并不影响这种行为反应。这些数据表明，LS及其与腹侧海马的连接在社交失败诱导的情绪后遗症中起优先作用。此外，位于LS内的GR在调节这种情绪状态中起重要作用。
