成大(陸汝斌) Memantine 用於 海洛因成癮

阿症老藥新用 可治海洛因成癮 11:32:19 （中央社記者龍瑞雲台北17日電）物質成癮已成為全球主要健康問題，成大醫學院與美國共同合作研發，用阿茲海默藥物以老藥新用模式，治療海洛因成癮者。國家衛生研究院、行政院衛生署與美國加州大學洛杉磯分校今天共同主辦「2013物質成癮防治國際會議」，由成大醫院精神科特聘教授陸汝斌發表最新毒癮治療模式研究成果。陸汝斌說，自二次世界大戰後海洛因在全球氾濫，有「默默的第三次世界大戰」之稱，不過至今卻無有效的治療海洛因成癮問題，成癮與基因有關、為何成癮與腦部退化仍不知，而這也是目前無法克服的。陸汝斌說，海洛因會造成什麼犯罪行為是最重要且應重視的問題，成大醫學院與美國國家衛生研究院、美國環境衛生總署共同合作，已完成最新毒癮治療模式。陸汝斌說，目前治療海洛因成癮問題是透過類似海洛因物質的美沙冬降低海洛因成癮性，屬於替代性療法，不過這是無法戒斷的。他說，最新研究成果是以「老藥新用」模式，以治療阿茲海默症用藥「Memantine」合併美沙冬替代療法，可有效降低對美沙冬的依賴並修補使用毒品後對腦部及身體所造成的傷害，這個新模式機制已經取得美國專利。1020417

Memantine abolishes the formation of cocaine-induced conditioned place preference possibly via its IL-6-modulating effect in medial prefrontal cortex. Behav Brain Res. 2011 Jun 20;220(1):126-31. In this study, we decided to use low doses of memantine pretreatment to examine the roles of the immune function in cocaine-supported conditioning. Cocaine-induced conditioned place preference (CPP) was used to assess the hedonic value and/or reinforcing efficacy of cocaine and cocaine-supported conditioning. Systemic pretreatment with memantine (20, 2.0, 0.2, and 0.02 mg/kg/injection) 30 min before each cocaine and saline conditioning trial abolished the acquisition of cocaine-induced CPP in mice. Even a total of 0.12 mg/kg memantine pretreatment in three days was effective in diminishing cocaine-induced CPP. Three consecutive days of cocaine conditioning increased interleukin-6 (IL-6) but decreased tumor necrosis factor (TNF-α) levels in medial prefrontal cortex (mPFC) and nucleus accumbens (Acb). Interestingly, pretreatment with memantine at the lowest effective dose (0.02 mg/kg/injection) reversed cocaine conditioning-enhanced IL-6 and -decreased TNF-α levels in these brain regions. Nevertheless, such a memantine dosing regimen did not affect dopamine metabolism in mPFC and Acb. Single memantine (0.02 mg/kg) injection did not acutely affect mouse locomotor activity or cocaine-increased locomotor activity. Similar memantine dosing regimen was ineffective to affect the maintenance of cocaine-induced CPP. Finally, intra-mPFC infusion of recombinant IL-6, but not thalidomide, reversed memantine (0.02 mg/kg/injection × 6)-decreased cocaine-induced CPP. These results, taken together, suggest that cocaine conditioning-enhanced IL-6 in mPFC may be, in part, involved in the acquisition of cocaine-induced CPP. Moreover, an extremely low dose of memantine may decrease the acquisition of cocaine-induced CPP by reversing cocaine conditioning-increased IL-6 levels in mPFC.