Hosseinmardi Narges, Fathollahi Yaghoub, Naghdi Nasser, Javan Mohammad
Department of Physiology, School of Medical Sciences, Tarbiat Modares University, PO Box: 14115-111, Tehran, Iran.
Brain Res. 2009 Nov 3;1296:1-14. doi: 10.1016/j.brainres.2009.08.020. Epub 2009 Aug 15.
The effects of chronic morphine exposure on synaptic plasticity in the CA1 region of the hippocampal slice preparation using extracellular recordings of the population spike (PS) evoked in response to Schaffer collateral stimulation were studied. High frequency stimulation (HFS; 1X100 Hz) and theta pulse stimulation (TPS; 5 Hz trains for 3 min) were used as patterned activities. The results showed that in rats chronically treated with morphine (dependent group), TPS induced long-term depression (LTD) of PS in CA1 in the absence of in vitro morphine. This TPS-induced PS LTD was blocked in the presence of either AP5 (NMDAR antagonist) or CPX (A1 adenosine receptor antagonist) alone, but was not blocked when AP5 and CPX were co-applied. This TPS-induced PS LTD was also blocked in the presence of either 8-PT (a selective A1 adenosine receptor antagonist) or MRS1220 (a specific A3 receptor antagonist). Additionally, when TPS was applied prior to HFS, PS long-term potentiation (LTP) was blocked. However, when TPS was applied after HFS, there was no reversal of PS LTP in slices from dependent rats in contrast to controls which displayed reversal of LTP. Both the PS LTD and the absence of PS LTP reversal were blocked by in vitro application of morphine. It is concluded that morphine withdrawal was associated with greater depression of CA1 PS elicited by natural stimulus induced activity pattern. This effect was associated with changes in NMDA and adenosine receptors due to chronic morphine administration. Such an in vitro preparation could provide a novel paradigm to investigate withdrawal effects on synaptic plasticity.
利用细胞外记录海马脑片制备中CA1区群体峰电位（PS）对Schaffer侧支刺激的反应，研究了慢性吗啡暴露对突触可塑性的影响。高频刺激（HFS；1×100Hz）和θ脉冲刺激（TPS；5Hz串刺激3分钟）用作模式化活动。结果显示，在慢性给予吗啡的大鼠（依赖组）中，在无体外吗啡的情况下，TPS诱导CA1区PS的长时程抑制（LTD）。单独使用AP5（NMDAR拮抗剂）或CPX（A1腺苷受体拮抗剂）时，这种TPS诱导的PS LTD被阻断，但当AP5和CPX联合应用时则未被阻断。这种TPS诱导的PS LTD在单独存在8-PT（选择性A1腺苷受体拮抗剂）或MRS1220（特异性A3受体拮抗剂）时也被阻断。此外，当在HFS之前施加TPS时，PS长时程增强（LTP）被阻断。然而，当在HFS之后施加TPS时，与显示LTP反转的对照组相比，依赖大鼠脑片中的PS LTP没有反转。PS LTD和PS LTP反转缺失均被体外应用吗啡所阻断。结论是，吗啡戒断与自然刺激诱导的活动模式引起的CA1区PS更大程度的抑制有关。这种效应与慢性给予吗啡导致的NMDA和腺苷受体变化有关。这样的体外制备可以为研究戒断对突触可塑性的影响提供一种新的范例。
