中文摘要：

海马是与阿片类物质依赖发生密切相关的脑组织之一.目前对海马组织参与阿片类物质依赖产生的机理仍缺乏认识.我们的研究发现,吗啡处理可通过改变cAMP/PKA信号通路调节海马神经元Na^＋,K^＋-ATPase活性,慢性暴露小鼠于吗啡可导致海马神经元Na^＋,K^＋-ATPase活性显著降低.以前的研究表明,Na^＋,K^＋-ATPase活性下降引起的神经元去极化参与了吗啡耐受和依赖作用的形成.另一方面,我们的研究也发现慢性吗啡处理可引起小鼠海马组织中与能量代谢相关的酶或辅酶表达显著降低,导致海马组织糖代谢功能的削弱.深入的研究表明海马组织糖代谢功能障碍参与了吗啡依赖的形成.因此,抑制海马神经元Na^＋,K^＋-ATPase活性和降低海马组织中与能量代谢相关的酶或辅酶表达可能与慢性吗啡处理引起的小鼠吗啡依赖的形成有关.

英文摘要：

Accumulating evidence has demonstrated that the hippocampus contributes to the development of opioid dependence. However, the mechanisms underlying the role of the hippocampus in opioid dependence are to be determined. Here, we demonstrated that chronic exposure of mice to morphine for 10 days resulted in a significant attenuation of Na^＋ , K^＋ - ATPase activity via upregulation of cAMP/PKA signal pathway. Given the previous findings that the depolarization of neurons induced by impairment of Na^＋, K^＋ - ATPase activity is involved in the development of opioid dependence, these findings suggest that diminution of Na^＋ , K^＋ - ATPase mediated by up - regulated cAMP/PKA cascade may be a potential mechanism underlying opioid dependence. In addition, we also found that chronic morphine treatment led to a remarkable down -regulation of the protein level of three energy metabolism enzymes. The failure of conversion of glucose into ATP was also observed in the chronic morphine- treated but not acute morphine- treated mice hippocampus. Intra- hippocampal injection of D - glucose but not non - metabolizable sugar 3 - O - methyl - glucose prior to morphine administration significantly suppressed naloxone - precipitated withdrawal jumping in acute morphine- treated mice. However, intra - hippocampal injection of glucose was unable to suppress naloxone - precipitated withdrawal jumping in chronic morphine - treated mice. These results demonstrated that the down- regulations of the hippocampal energy metabolism protein expression and impairment of glucose metabolism were also involved in the development of morphine dependence.