Low-dose memantine attenuated morphine addictive behavior through its anti-inflammation and neurotrophic effects in rats

Shiou Lan Chen, Pao Luh Tao, Chun Hsien Chu, Shih Heng Chen, Hsiang En Wu, Leon F. Tseng, Jau Shyong Hong, Ru Band Lu

研究成果: Article同行評審

64 引文 斯高帕斯(Scopus)


Opioid abuse and dependency are international problems. Studies have shown that neuronal inflammation and degeneration might be related to the development of opioid addiction. Thus, using neuroprotective agents might be beneficial for treating opioid addiction. Memantine, an Alzheimer's disease medication, has neuroprotective effects in vitro and in vivo. In this study, we evaluated whether a low dose of memantine prevents opioid-induced drug-seeking behavior in rats and analyzed its mechanism. A conditionedplace- preference test was used to investigate the morphineinduced drug-seeking behaviors in rats. We found that a lowdose (0.2-1 mg/kg) of subcutaneous memantine significantly attenuated the chronic morphine-induced place-preference in rats. To clarify the effects of chronic morphine and low-dose memantine, serum and brain levels of cytokines and brainderived neurotrophic factor (BDNF) were measured. After 6 days of morphine treatment, cytokine (IL-1β, IL-6) levels had significantly increased in serum; IL-1β and IL-6 mRNA levels had significantly increased in the nucleus accumbens and medial prefrontal cortex, both addiction-related brain areas; and BDNF levels had significantly decreased, both in serum and in addiction-related brain areas. Pretreatment with low-dose memantine significantly attenuated chronic morphine-induced increases in serum and brain cytokines. Low-dose memantine also significantly potentiated serum and brain BDNF levels.We hypothesize that neuronal inflammation and BDNF downregulation are related to the progression of opioid addiction. We hypothesize that the mechanism low-dose memantine uses to attenuate morphine-induced addiction behavior is its anti-inflammatory and neurotrophic effects.

頁(從 - 到)444-453
期刊Journal of Neuroimmune Pharmacology
出版狀態Published - 2012 6月

All Science Journal Classification (ASJC) codes

  • 神經科學(雜項)
  • 免疫學和過敏
  • 免疫學
  • 藥理


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