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    题名: Mephedrone (4-甲基甲基卡西酮) 對大鼠制約地點偏好的影響
    Effect of Mephedrone (4-methylmethcathinone, 'meow') on Conditioned Place Preference in Rats
    作者: 陳賢修;Chen, XianXiu
    贡献者: 公共衛生學系碩士班
    关键词: Mephedrone;4-Methylmethcathinone;4-甲基甲基卡西酮;條件化行為;制約性地點偏好;Mephedrone;4-Methylmethcathinone;Conditioned Place Preference;CPP
    日期: 2012-07-26
    上传时间: 2012-08-31 16:28:45 (UTC+8)
    出版者: 中國醫藥大學
    摘要: 背景 / 目的：
    Mephedrone之化學名為4-methylmethcathinone(4-甲基甲基卡西酮)(4-MMC)，施用後有欣快、興奮等作用，會產生類似甲基安非他命與搖頭丸的效果，但因作用時間短，故施用者會不斷追加劑量。新興合成物質mephedrone的濫用已逐漸在全世界蔓延，目前mephedrone相關的藥物資料並不多,多半是來自濫用者的自我報告或是急診室的病歷紀錄，而不是實驗研究。這個實驗利用制約地點偏好(CPP)的模式來探討4-甲基甲基卡西酮(mephedrone)對大鼠的影響 。
    方法：
    本試驗利用公SD 大鼠及制約性地點偏好 (Conditioned Place Preference)標準協定的動物模式，探討mephedrone的藥物成癮性與劑量反應測試。試驗分成給予生理食鹽水的控制組及四組給予不同mephedrone劑量的實驗組(5 mg/kg, 10 mg/kg, 20 mg/kg and 40 mg/kg)，每組各3隻。體重的測量分別是在試驗開始的第一天(習慣期)，及每次藥物給予前(條件化期)。偏好的變化是計算條件化前後，大鼠停留在給予藥物的那個空間的時間差(以秒計算)。並以重複量數單因子變異數分析統計其差異。
    結果：
    給予生理食鹽水的控制組及四組給予不同mephedrone劑量的實驗組的體重增長並沒有顯著差異。於停留在給予藥物之空間的時間上，條件化前(第三天)五組皆無顯著差異(5 mg/Kg P=1; .10 mg/Kg P=0.674; 20 mg/Kg P=0.876; 40 mg/Kg P=0.975)。條件化後(第11天)，給予低劑量mephedrone的兩組相較於給予生理食鹽水的控制組，並無顯著差異(5 mg/Kg P=0.893; 10 mg/Kg P=0.804)，然而，在給予高劑量mephedrone的兩組，相較於給予生理食鹽水的控制組，卻有很顯著的差異(20 mg/Kg P=0.012; 40 mg/Kg P=0.001)。
    結論：
    結果呈現當老鼠急性、重複每日暴露於高劑量的mephedrone，會出現酬償性反應。這個結果反映出mephedrone可能會有藥物依賴的成癮反應產生。至於確切的劑量、藥物給予次數、藥物需求間隔及戒斷反應，還有其分子生物訊號與藥物影響途徑，則是我們下一步要努力的目標。
    Background / Purpose :
    Mephedrone, also known as 4-methylmethcathinone (4-MMC), or 4-methylephedrone, is a synthetic stimulant drug of the amphetamine and cathinone classes. Mephedrone is hypothesized to possess abuse liability, abuse of the dangerous street drug has become commonplace in the Europe and United States, which has caused many deaths in Europe. Knowledge about the pharmacology of mephedrone has been obtained primarily from surveys of drug abusers and emergency room visits rather than experimental studies. The present study used the conditioned place preference (CPP) assays to investigate behavioral effects of mephedrone.
    Methods :
    An unbiased place conditioning protocol was used to examine the expression of the rewarding effects of mephedrone and related dose response. Male Sprague–Dawley rats were used in this experiment. Rats were divided into five groups, saline controlled group and four different doses of mephedrone treated groups (5 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg), three rats in each group. The body weight of rats was taken on the beginning of the habituation phase (day 1) and before the mephedrone injection during the conditioning phase. The change of preference was calculated as the difference (in seconds) between the time spent in the drug-paired compartment on the testing day and the time spent in this compartment in the pre-conditioning session. One-way, ANOVA, repeated measures were used to analyse the differences.
    Results :
    The mean body weight gain showed no significant difference among the saline controlled group and four mephedrone treated groups. The mean differences of the time spent in the drug-paired compartment of the five groups had no significant differences in day 3 (pre-conditioning) (5 mg/Kg P=1; .10 mg/Kg P=0.674; 20 mg/Kg P=0.876; 40 mg/Kg P=0.975). At day 11 (post-conditioning), there was no significant difference among low doses (5 mg/Kg P=0.893; 10 mg/Kg P=0.804), while with significant difference among high doses (20 mg/Kg P=0.012; 40 mg/Kg P=0.001) when they were compared with the saline controlled group.
    Conclusion :
    Our results indicated that previous repeated mephedrone exposure enhanced subsequent CPP drug reward behavior.
    Future studies that various factors such as dose, dosing frequency, and forced abstinence interval are needed to further assess the motor activating properties of mephedrone. Furthermore, we will examine phosphorylation levels of various relevant signaling molecules in the brain regions implicated in addictive behaviors after acute and repeated mephedrone administration.
    显示于类别:[公共衛生學系暨碩博班] 博碩士論文

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