吗啡和二氢埃托啡对大鼠不同脑区单胺递质含量的影响

用脑微透析方法观察阿片受体激动剂吗啡和二氢埃托啡（ＤＨＥ）对麻醉大鼠不同脑区单胺递质释放的影响．吗啡２０ｍｇ·ｋｇ－１ｓｃ单次给药可使脑纹状体内多巴胺和５－羟色胺的代谢产物３，４－二羟基苯乙酸（ＤＯＰＡＣ）和５－羟吲哚乙酸（５－ＨＩＡＡ）的浓度分别增加４７％和４６％；丘脑和蓝斑区去甲肾上腺素（ＮＥ）的释放减少２５％和３２％．ＤＨＥ２μｇ·ｋｇ－１ｓｃ除丘脑ＮＥ的释放明显减少约４０％外，对其他脑区单胺递质的释放均无明显影响．吗啡２０－１００ｍｇ·ｋｇ－１ｓｃ，每日２次，或ＤＨＥ２－１０μｇ·ｋｇ－１ｓｃ，每日４次，逐日递增，连续给药５ｄ使大鼠产生依赖后，上述变化明显减少或消失．但用纳络酮１ｍｇ·ｋｇ－１ｉｖ催促戒断时，吗啡依赖大鼠脑蓝斑区ＮＥ和中缝核区５－ＨＩＡＡ的浓度迅速增加至１４６％和１９８％．ＤＨＥ依赖大鼠纹状体内ＤＯＰＡＣ和５－ＨＩＡＡ的浓度分别增加约９０％和３０％．但对蓝斑ＮＥ的释放无明显影响．结果表明吗啡和ＤＨＥ在中枢的作用部位有差异，而且这种差异可能是导致两药躯体依赖性不同的重要原因之一．

Effects of morphine and dihydroetorphine on content of monoamine transmitter in the different brain regions of rats

The effects of morphine and dihydroetophine (DHE) on monoamine transmitter release in the different brain regions of anaesthetized rats were studied by microdialysis following an acute and chronic treatment as well as naloxone-precipitated withdrawal. The results showed that the extracellular concentrations of 3,4-dihydro- xyphenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid(5- HIAA) in striatum were increased about 47% and 46% over baseline; nor-epinephrine (NE) concentration in locus coeruleus (LC) and thalamus were decreased about 32% and 25%, respectively after acute treatment with morphine 20 mg·kg^-1 sc. No significant change in monoamine transmitter release was measured in the rats treated with DHE 2 μg·kg^-1 sc., except for a decrease in NE concentration in the thalamus about 40%. But in morphine or DHE dependent rats, the above mentioned changes in monoamine transmitter release were reduced or disappeared. However, in the morphine-dependent rats, naloxone (1 mg·kg^-1 iv) suddenly increased NE concentration in LC to 146% and 5- HIAA concentration to 198% of pre drug level. In contrary, naloxone had no effect on NE release in LC of DHE- dependent rats but rose the extracellular concentration of DOPAC and 5- HIAA in striatum about 90% and 30%, respectively during naloxone- precipitated withdrawal. These results demonstrate that the brain regions to which DHE acts are different from that of morphine, which may be one of the major reasons resulted in distinct abstinence syndrome between morphine and DHE.