Spinal amino acid release and repeated withdrawal in spinal morphine tolerant rats
Spinal amino acid release and repeated withdrawal in spinal morphine tolerant rats
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DOI：
10.1038/sj.bjp.0705102
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发表时间：
2003-02-01
影响因子：
7.3
通讯作者：
Yaksh, TL
中科院分区：
文献类型：
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作者：
Ibuki, T;Marsala, M;Yaksh, TL
1我们在清醒大鼠中使用脊髓微透析来研究在持续脊髓输注吗啡期间反复戒断纳洛酮是否会导致脊髓谷氨酸释放逐渐增加和更明显的鞘内耐受。2大鼠接受腰椎鞘内（IT）输注吗啡（IT-M：20 nmol穆尔（-1）h（-1））或生理盐水（IT-S：1穆尔h（-1））连续给药3天。将两组进一步细分以接受腹膜内（i. p.）注射纳洛酮（IP-N：0.6 mg kg（-1））或生理盐水（IP-S：3 ml kg（-1）），每24小时后开始IT输注。测量每日热逃逸潜伏期、戒断体征、IP注射前静息基础脊髓氨基酸释放和注射后立即释放（诱发）。3接受IT吗啡的大鼠在第1天显示热逃逸潜伏期最大增加，之后该值下降，其中IT吗啡+ IP纳洛酮组下降最快。在第1天，各组之间在静息基础氨基酸释放方面没有观察到显著差异。IT吗啡+i. p.纳洛酮组的大鼠显示该值进行性增加。其他组的释放没有显著改变。4对于IT-M + IP-N组，Glu、Asp和Tau的基础静息透析液浓度在3天输注间隔内稳定上升。任何其他处理均未观察到基础静息释放的变化。5 IT-M动物的诱发释放（i. p.纳洛酮后）在三次重复暴露中显示出进行性增加。诱发释放在其他治疗组中没有显著变化。6沉淀戒断的程度与腹膜内注射急性诱发的谷氨酸增加显著相关。7目前的结果表明，脊髓阿片激动剂活性的周期性短暂戒断导致谷氨酸流出和戒断体征的进行性增加，其方式与脊髓耐受性的增强发展一致。
1 We used spinal microdialysis in awake rats to investigate whether the repeated withdrawal with naloxone during continuous spinal infusion of morphine would lead to a progressively greater spinal glutamate release and a more pronounced intrathecal tolerance.2 Rats received lumbar intrathecal (IT) infusion of morphine (IT-M: 20 nmol mul(-1) h(-1)) or saline (IT-S: 1 mul h(-1)) continuously for 3 days. Both groups were further subdivided to receive intraperitoneal (i.p.) injection of naloxone (IP-N: 0.6 mg kg(-1)) or saline (IP-S: 3 ml kg(-1)) every 24 h after the beginning of IT infusion. Daily thermal escape latencies, withdrawal signs, the resting basal release of spinal amino acids before IP injection and the release immediately after the injection (evoked) were measured.3 Rats receiving IT morphine showed a maximum increase in thermal escape latency on day 1, after which this value declined, with the fastest decline observed in IT morphine + IP naloxone group. On day 1, no significant difference was observed among groups in the resting basal release of amino acids. Rats in IT morphine+ i.p. naloxone group displayed a progressive increase in this value. The release was not significantly altered in other groups.4 For the IT-M + IP-N group, basal resting dialysate concentrations of Glu, Asp and Tau rose steadily over the 3-day infusion interval. No change in basal resting release was noted for any other treatment.5 Evoked release (after i.p. naloxone) in IT-M animals displayed a progressive increase over the three repeated exposures. Evoked release did not change significantly in other treatment groups.6 The degree of precipitated withdrawal significantly correlated with the increase in glutamate acutely evoked by i.p. injection.7 The present results show that periodic transient withdrawal of spinal opiate agonist activity leads to a progressive increase in glutamate outflow and withdrawal signs, in a manner consistent with an enhanced development of spinal tolerance.