摘要 本研究首先探討黃連甲醇粗抽物及其活性成分小蘗鹼於強迫游泳試驗法及尾部懸吊試驗法之抗憂鬱作用，並以小蘗鹼併用臨床常用抗憂鬱藥物desipramine、maprotiline、fluoxetine與moclobemide，探討小蘗鹼之抗憂鬱劑機轉。最後並測定小鼠腦組織紋狀體、海馬回與皮質組織中神經傳導物質：血清素(serotonin)、正腎上腺素(norepinephrine)、多巴胺(dopamine)及其代謝物的濃度，以探討小蘗鹼抗憂鬱作用機轉與腦內各部位神經傳導物質的關係。 實驗結果發現，黃連甲醇粗抽物 (0.1, 0.5 g/kg)及其活性成分小蘗鹼 (0.02 g/kg)均可減少強迫游泳試驗的漂浮不動時間。而在尾部懸吊試驗中，黃連甲醇粗抽物(0.1, 0.5 g/kg)，及其活性成分小蘗鹼(0.02 g/kg)均可明顯減少小鼠尾部懸吊引起之靜止不動時間。 在小蘗鹼併用臨床常用之抗憂鬱藥物之研究結果發現，小蘗鹼(0.02 g/kg)併用desipramine(20 mg/kg)對小鼠在強迫游泳試驗中漂浮不動的時間，較單獨使用desipramine的漂浮不動時間有顯著縮短。小蘗鹼(0.02 g/kg)併用maprotiline、fluoxetine與moclobemide對小鼠在強迫游泳試驗不動的時間，與單獨使用maprotiline、fluoxetine與moclobemide不動的時間相比並無明顯差異。 其次，在測定小鼠腦內單胺濃度實驗，小蘗鹼(0.02, 0.1 g/kg)對紋狀體中多巴胺的含量有增加作用；在海馬回，小蘗鹼(0.02 g/kg)對血清素及正腎上腺素的含量有增加的作用；在皮質，小蘗鹼(0.02 g/kg)亦會增加血清素及正腎上腺素的含量。 綜合以上結果顯示，黃連甲醇粗抽物及其活性成分小蘗鹼不論在強迫游泳試驗或在在尾部懸吊實驗，均有明顯的抗憂鬱作用，小蘗鹼之抗憂鬱轉可能與提升腦內中海馬迴及皮質的血清素及正腎上腺素及紋狀體的多巴胺的含量有關。; Abstract In the present study, we investigated the anti-depressant effect of methanol extract of Coptidiis Rhizoma (CR MeOH)and berberine by using forced swimming test (FST) and tail suspension test (TST). We also investigated the mechanism of action of antidepression of berberine by combining with the desipramine (tricyclic antidepressant), maprotiline (selective NA uptake inhibitor), fluoxetine (selectives erotonin reuptake inhibitors) and moclobemide (monoamine oxidase A inhibitors). Then we further measured norepinephrine, serotonin, dopamine and its metabolites levels in mice striatum, hippocampus and cortex to understand the mechanism of the anti-depressive effect. The results shown that methanol extract of CR MeOH (0.1, 0.5 g/kg) and berberine (0.02 mg/kg ), significantly reduce the immobility time during the forced swimming test .CR MeOH(0.1, 0.5 g/kg) and berberine (0.02 mg/kg) significantly inhibited immobility time during the tail suspension test. Berberine could significantly decrease the immobility time induced by desipramine, maprotiline and moclobemide, and did not affect the immobility time induced by fluoxetine. Futhermore, berberine increased norepinephrine and serotonin level in the hippocampus and cortex and dopamine level in the striatum. Our findings support the view that CR MeOH and berberine exerts anti-depressive effects. The anti-depressive mechanism of berberine may be related to the increase in norepinephrine and serotonin levels in the hippocampus and cortex, dopamine level in the striatum.
