Martin P, Pichat P, Massol J, Soubrié P, Lloyd K G, Puech A J
Département de Pharmacologie, Faculté de Médecine Pitié-Salpêtrière, Paris.
Neuropsychobiology. 1989;22(4):220-4. doi: 10.1159/000118620.
Recently, sufficient evidence has accumulated to suggest that a central GABAergic dysfunction may be primarily related to the physiopathology of affective disorders and that antidepressant mechanisms have an intrinsic GABAergic component. In depressed patients GABA levels are reported to be low in the cerebral spinal fluid and plasma, and GABA synthesis is decreased in some brain areas, including the frontal cortex. GABA mimetics exhibit antidepressant-like actions in behavioral models in the olfactory bulbectomized rat and in the learned helplessness paradigm. In the olfactory bulbectomized rat, GABA B receptors are down regulated in the frontal cortex and in the learned helplessness paradigm, GABA release is diminished in the hippocampus. These decreases are reversed by antidepressants in parallel with their behavioral activities. In this study, data obtained indicate that in the learned helplessness paradigm, GABA B receptors are decreased in the frontal cortex and this decrease is reversed by imipramine and desipramine (16 mg/kg/day) in animals which are considered to be 'responders' to antidepressant treatments.
最近，已有足够的证据表明，中枢γ-氨基丁酸（GABA）能功能障碍可能主要与情感障碍的生理病理学相关，且抗抑郁机制具有内在的GABA能成分。据报道，抑郁症患者脑脊液和血浆中的GABA水平较低，包括额叶皮质在内的一些脑区的GABA合成减少。GABA模拟物在嗅球切除大鼠的行为模型和习得性无助范式中表现出抗抑郁样作用。在嗅球切除大鼠中，额叶皮质中的GABA B受体下调；在习得性无助范式中，海马体中的GABA释放减少。这些减少与抗抑郁药的行为活性平行，可被抗抑郁药逆转。在本研究中，获得的数据表明，在习得性无助范式中，额叶皮质中的GABA B受体减少，而在被认为是抗抑郁治疗“反应者”的动物中，丙咪嗪和去甲丙咪嗪（16毫克/千克/天）可逆转这种减少。
