類嗎啡類(opioids)成癮之療法，目前皆著重於以單一類嗎啡藥物來進行治療，然而影響其成癮之因素很多，其中精神因素即佔了重要的一部份，因此若能以治療精神疾病之藥物如選擇性血清素再回收抑制劑(selective serotonin reuptake inhibitors; SSRIs)來作為輔助療法之藥物，將有可能加強原本藥物之療效並減輕其戒斷症狀。 在本研究中我們擬擴大研究，探討以SSRIs應用於減輕嗎啡戒斷反應及其藥效機轉。本研究共分成二年：第一年建立以微透析高效能液相層析法，分析腦中指標神經傳導物質及其代謝物之變化，確認其與減輕嗎啡戒斷反應之相關性及其動物模式。第二年廣泛地探討SSRIs對於具有嗎啡身體依賴性動物在戒斷上之療效(single use)，找出最佳之三個藥物，並作出劑量和反應之相關性。 我們現在繳交第一年研究報告，我們皆依原定計畫之規劃，完成了應有之進度。除已建立相關動物模式外，並已完成10種指標神經傳導物質及其代謝物之分析方法。 The treatments of opioid addiction focus on the single use of opioids presently. However, there are many opioid addiction-associated factors, among which a psychological factor plays an important role. If selective serotonin reuptake inhibitors (SSRIs, a psychosis drug) are applied for an auxiliary treatment, the effect of the main medicine can be enhanced and the withdrawal symptoms reduced. In this study, the efficacy and mechanism of SSRIs in reducing morphine-withdrawal symptoms will be further investigated. The study takes 2 years. In the first year, an animal model and the target neurotransmitter and metabolite levels in brain are set up by using microdialysis coupled with HPLC-ECD to evaluate the efficacy of SSRIs. In the second year, an estivative model is set up to discover the three most effective drugs and the association among their dose-response curves. Now we report the results in the firt year. We have done everything in the first on schedule. A series of animal models were developed and an analytic method to determine ten target neurotransmitter and metabolite levels in brain was set up.
