Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran.
Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Brain Behav. 2024 Oct;14(10):e70043. doi: 10.1002/brb3.70043.
The infralimbic (IL) subregion of the medial prefrontal cortex (mPFC) regulates the extinction of conditioned fear memory. Glucocorticoid and gamma-aminobutyric acid (GABA) receptors are expressed in the mPFC and are also critical in fear extinction. This study investigated the possible interactive effects of the glucocorticoids and GABAergic system in the IL on the regulation of fear extinction.
The rats were trained using an auditory fear conditioning task during which they received three conditioned stimuli (tones, 30 s, 4 kHz, 80 dB), co-terminated with the three unconditioned stimuli (footshock, 0.8 mA, 1 s). Extinction testing was conducted over 3 days (Ext 1-3). Thirty minutes before the first extinction trial (Ext 1), the rats received bicuculline (BIC, 1 mg/kg/2 mL, intraperitoneal [i.p.]) as a GABA receptor antagonist or CGP55845 (CGP, 0.1 mg/kg/2 ML, i.p.) as a GABA receptor antagonist followed by systemic injection of corticosterone (CORT, 3 mg/kg/2 ML, i.p.). Furthermore, separate groups of rats received a bilateral intra-IL injection of BIC (100 ng/0.3 µL/side) or CGP (10 ng/0.3 µL/side) followed by a systemic injection of CORT (3 mg/kg/2 ML, i.p.) before the first extinction trial (Ext 1). The extracellular signal-regulated kinase (ERK1) and cAMP response element-binding (CREB) activity in the IL was examined by Western blot analysis after Ext 1.
The results indicated that systemic CORT injection facilitated fear extinction and increased the expression of ERK1 but not CREB in the IL. Both systemic and intra-IL co-injection of BIC or CGP blocked the effects of CORT on fear extinction and ERK1 expression.
These findings suggest that glucocorticoids and the GABAergic system may modulate fear extinction through the ERK pathway in the IL.
内侧前额叶皮层（mPFC）的下边缘区域（IL）调节条件性恐惧记忆的消退。糖皮质激素和γ-氨基丁酸（GABA）受体在 mPFC 中表达，并且在恐惧消退中也很关键。本研究调查了 IL 中的糖皮质激素和 GABA 能系统之间可能的相互作用对恐惧消退的调节作用。
使用听觉恐惧条件反射任务对大鼠进行训练，在此期间，它们接受三个条件刺激（音调，30s，4kHz，80dB），与三个非条件刺激（电击，0.8mA，1s）同时终止。在 3 天内进行消退测试（Ext 1-3）。在第一次消退试验（Ext 1）前 30 分钟，大鼠接受荷包牡丹碱（BIC，1mg/kg/2mL，腹腔内 [i.p.]）作为 GABA 受体拮抗剂或 CGP55845（CGP，0.1mg/kg/2ML，i.p.）作为 GABA 受体拮抗剂，然后全身注射皮质酮（CORT，3mg/kg/2ML，i.p.）。此外，另有几组大鼠在第一次消退试验（Ext 1）前接受双侧 IL 内注射 BIC（100ng/0.3µL/侧）或 CGP（10ng/0.3µL/侧），然后全身注射 CORT（3mg/kg/2ML，i.p.）。在 Ext 1 后通过 Western blot 分析检查 IL 中的细胞外信号调节激酶（ERK1）和 cAMP 反应元件结合（CREB）活性。
结果表明，全身 CORT 注射促进了恐惧消退，并增加了 IL 中 ERK1 的表达，但不增加 CREB 的表达。全身和 IL 内共注射 BIC 或 CGP 阻断了 CORT 对恐惧消退和 ERK1 表达的影响。
这些发现表明，糖皮质激素和 GABA 能系统可能通过 IL 中的 ERK 途径调节恐惧消退。
