近年來有越來越多的證據支持古柯鹼成癮的機制是透過產生神經適應而來，這種神經適應涉及獲得古柯鹼時相關線索的學習及記憶過程。而有許多研究指出免疫系統涉及學習及記憶的形成過程。我們先前的研究證明注射古柯鹼會增加前發炎因子-細胞刺激素及趨化素分泌。此篇研究假設免疫系統的活性涉及古柯鹼成癮時的學習及記憶的形成過程。臨床研究顯示memantine藉由降低微小膠細胞相關的發炎反應與刺激星狀膠細胞釋出神經營養因子而改善阿茲海默氏症引起的記憶力缺損。Lipopolysaccharides (LPS)是格蘭氏陰性菌細胞膜表面的脂多醣體，會引發生物體強烈的發炎反應。此篇研究藉由訓練小鼠古柯鹼場地制約偏好前給予此二種藥物以研究它們後續的影響及對古柯鹼場地制約偏好引發的調節效果。我們發現當給予低劑量的memantine前治療時會消減古柯鹼場地制約偏好，此種效果是透過扭轉了在前額葉及紋狀體發現的古柯鹼制約導致的介白質-6上升現象與古柯鹼制約導致的腫瘤壞死因子-α下降現象。

A growing body of evidence supports the notion that cocaine addiction produces neuronal adaptations involving a process of learning and memory to cocaine-associated cues. Studies have demonstrated immune system is involved in such a learning and memory process. Our previous study suggests that cocaine injection can increase proinflammatory cytokines and chemokine secretion. The hypothesis of this study was that the immune activation may be involved in forming the learning and memory of cocaine addiction. Clinical studies revealed that memantine may attenuate memory defect of Alzheimer’s disease by reducing microglia-associated inflammation and stimulating neurotrophic factor release from astroglia, a central immune cell. Lipopolysaccharides (LPS), a component on the outer membrane of Gram-negative bacteria, can elicit strong immune responses in brain.Thus, our objective was to investigate the modulating effect of memantine and LPS pretreatment on cocaine-induced conditioned place preference (Coc-CPP). We found that low-dose memantine pretreatment abolished the magnitude of Coc-CPP via reversing cocaine conditioning-enhanced IL-6 and -decreased TNF-α levels in the prefrontal cortex and striatum.

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