Pobbe Roger L H, Zangrossi Helio
Department of Pharmacology, School of Medicine, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, Brazil, CEP: 14049-900.
Life Sci. 2008 Jun 20;82(25-26):1256-61. doi: 10.1016/j.lfs.2008.04.012. Epub 2008 May 1.
Recently obtained evidence points to the involvement of the lateral habenular nuclei (LHb) in the mediation of coping defensive responses to threatening/stressful stimuli. Nevertheless, the role of this brain area in the regulation of defensive responses that have been associated with specific subtypes of anxiety disorders recognized in clinical settings is presently unknown. To address this question, we investigated the effects of either electrolytic lesions or chemical stimulation of the LHb on the defensive behaviors generated in rats by the elevated T-maze. This experimental model allows the measurement, in a same rat, of two defensive behaviors, inhibitory avoidance and escape, that have been related in terms of psychopathology to generalized anxiety and panic disorders, respectively. Bilateral electrolytic lesions of the LHb (1 mA, 10 s) impaired inhibitory avoidance acquisition and facilitated escape performance. On the other hand, chemical stimulation of the LHb by bilateral microinjection of kainic acid (30-60 pmol/0.2 microL) had the opposite effect, i.e., facilitated inhibitory avoidance and impaired escape. The present results indicate that the LHb exerts an opposed regulatory control on generalized anxiety- and panic-related defensive responses in rats.
最近获得的证据表明，外侧缰核（LHb）参与了对威胁性/应激性刺激的应对防御反应的调节。然而，目前尚不清楚该脑区在调节与临床环境中公认的特定焦虑症亚型相关的防御反应中的作用。为了解决这个问题，我们研究了LHb的电解损伤或化学刺激对高架T迷宫在大鼠中产生的防御行为的影响。这个实验模型允许在同一只大鼠中测量两种防御行为，即抑制性回避和逃避，它们在精神病理学上分别与广泛性焦虑症和惊恐障碍相关。LHb的双侧电解损伤（1 mA，10 s）损害了抑制性回避的习得，并促进了逃避表现。另一方面，通过双侧微量注射 kainic 酸（30 - 60 pmol/0.2 μL）对LHb进行化学刺激则产生相反的效果，即促进抑制性回避并损害逃避。目前的结果表明，LHb对大鼠中与广泛性焦虑和惊恐相关的防御反应发挥相反的调节控制作用。
