Max-Planck-Institute for Psychiatry, Clinical Institute, Kraepelinstr. 2, D-8000 Munich 40, Germany.
J Psychopharmacol. 1992 Jan;6(2):265-72. doi: 10.1177/026988119200600220.
The in vivo effects of the anticonvulsant drug sodium valproate (VPA) on pre-optic gamma-aminobutyric acid (GABA) release and pituitary luteinizing hormone (LH) secretion were studied by perfusing the pre-optic area of unanaesthetized, freely moving ovarectomized rats through push-pull cannulae at a flow-rate of 20 >μl/min with a fraction period of 15 min. Local treatment with 40, 100, 400 and 1600 μg VPA/ml differently affected pre-optic GABA release and pituitary LH secretion concerning mean level, mean pulse amplitude and mean pulse frequency. GABA levels in perfusate were suppressed by local treatment with 40 and 100 μg VPA/ml CSF, respectively, whereas no significant change could be observed at the highest concentration used (1600 μg VPA/ml CSF). Pituitary LH secretion was reduced by pre-optic perfusion with 100 μg VPA/ml CSF with regard to mean plasma level and pulse amplitude but no significant change in pulse frequency could be observed. By raising VPA concentration the effects became more pronounced, and at 1600 μ g VPA/ml CSF there was a marked reduction of LH secretion regarding mean plasma level, amplitude and frequency. In conclusion, the present data put forward our view that the mechanism of action of VPA generates an enhancement of GABAergic transmission different from that involving elevated extracellular GABA.
体内研究抗惊厥药丙戊酸钠（VPA）对未麻醉、自由活动的卵巢切除术大鼠视前区γ-氨基丁酸（GABA）释放和垂体促黄体激素（LH）分泌的影响，通过推挽式灌流导管以 20 >μl/min 的流速，15 min 的分数期，向视前区进行局部处理。用 40、100、400 和 1600 μg VPA/ml 的局部处理分别影响视前区 GABA 释放和垂体 LH 分泌的平均水平、平均脉冲幅度和平均脉冲频率。局部处理 40 和 100 μg VPA/ml CSF 时，灌流液中的 GABA 水平分别受到抑制，而在使用的最高浓度（1600 μg VPA/ml CSF）时未观察到明显变化。视前区用 100 μg VPA/ml CSF 灌注时，LH 分泌减少，血浆水平和脉冲幅度均减少，但脉冲频率无明显变化。提高 VPA 浓度会使作用更加明显，而在 1600 μ g VPA/ml CSF 时，LH 分泌的平均血浆水平、幅度和频率明显降低。总之，本研究数据表明，VPA 的作用机制产生了不同于升高细胞外 GABA 的 GABA 能传递增强。
