Ferraro L, Tanganelli S, O'Connor W T, Antonelli T, Rambert F, Fuxe K
Institute of Pharmacology, University of Ferrara, Italy.
Neurosci Lett. 1996 Dec 6;220(1):5-8. doi: 10.1016/s0304-3940(96)13212-2.
The effect of modafinil on endogenous gamma-aminobutyric acid (GABA) release in the medial preoptic area (MPA) and posterior hypothalamus (PH) and the role of local 5-HT3 receptors in this effect was investigated in the awake rat using in vivo microdialysis. Modafinil (30-100 mg/kg i.p.) dose-dependently decreased GABA release from the MPA, while only the 100 mg/kg dose markedly reduced GABA release in the PH. The modafinil (100 mg/kg) induced inhibition of GABA release in the MPA and the PH was partially counteracted by the 5-HT3 receptor antagonist MDL72222 (1 microM) when perfused locally alone or together with the non-selective 5-HT receptor antagonist methysergide (1 microM). Thus, the reduction of GABA transmission induced by modafinil in the MPA and in the PH, at least in part, involves local 5-HT3 receptors. The GABA release inhibition by modafinil in the above areas may be relevant for its vigilance promoting action.
采用体内微透析技术，在清醒大鼠中研究了莫达非尼对内侧视前区（MPA）和下丘脑后部（PH）内源性γ-氨基丁酸（GABA）释放的影响，以及局部5-HT3受体在该效应中的作用。莫达非尼（30 - 100 mg/kg腹腔注射）剂量依赖性地降低了MPA中GABA的释放，而只有100 mg/kg剂量显著降低了PH中GABA的释放。当单独局部灌注或与非选择性5-HT受体拮抗剂美西麦角（1 microM）一起局部灌注时，莫达非尼（100 mg/kg）诱导的MPA和PH中GABA释放的抑制被5-HT3受体拮抗剂MDL72222（1 microM）部分抵消。因此，莫达非尼在MPA和PH中诱导的GABA传递减少至少部分涉及局部5-HT3受体。莫达非尼在上述区域对GABA释放的抑制作用可能与其促进警觉的作用有关。
