Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism.
Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism.
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发表时间：
1989-09
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通讯作者：
S. Sivam
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作者：
S. Sivam
研究了Sprague-Dawley大鼠急性（单次给药）或亚慢性（每天一次，持续4天）给予可卡因对纹状体脑啡肽（Met 5-脑啡肽）、纹状体黑质速激肽（P物质）和强啡肽[强啡肽A（1-8），DYN]水平的影响。通过放射免疫测定法测定肽水平。采用高效液相色谱电化学检测法测定纹状体多巴胺（DA）、5-羟色胺及其酸性代谢产物的浓度。急性给予可卡因（20或30 mg/kg i. p.）不影响纹状体或黑质中的肽水平。可卡因的亚慢性给药方案（20 mg/kg/天，持续4天）增加了纹状体黑质DYN水平，而不改变Met 5-脑啡肽或P物质的水平。DYN水平的增加持续至少4天后，最后一剂可卡因的亚慢性给药。DYN水平在末次给药后12天恢复至对照值。单剂量可卡因后30分钟，纹状体中的DA水平升高。其他处理均未引起DA或5-羟色胺或其代谢产物的任何变化。亚慢性可卡因给药多巴胺能去神经大鼠与6-羟基多巴胺未能引起纹状体或黑质中DYN水平的任何增加。与可卡因亚慢性方案同时给予D1 DA拮抗剂SCH-23390或D2 DA拮抗剂螺哌隆也可阻断可卡因诱导的DYN水平升高。这些结果表明，可卡因选择性地增强或减少纹状体黑质神经元DYN的合成或释放。（250字处删节）
The influence of the acute (single dose) or subchronic (one dose daily for 4 days) administration of cocaine to Sprague-Dawley rats on striatal enkephalin (Met5-enkephalin) and striatonigral tachykinin (substance P) and dynorphin [dynorphin A (1-8), DYN] levels was investigated. The peptide levels were determined by radioimmunoassay. The concentrations of the striatal levels of dopamine (DA), 5-hydroxytryptamine and their acid metabolites were determined by high-performance liquid chromatography with electrochemical detection. An acute administration of cocaine (20 or 30 mg/kg i.p.) did not affect the peptide levels in the striatum or in the substantia nigra. A regimen of subchronic administration of cocaine (20 mg/kg/day for 4 days) increased the striatonigral DYN levels, without altering the levels of Met5-enkephalin or substance P. The increase in DYN levels were persistent for at least 4 days after the last dose of the subchronic administration of cocaine. The DYN levels returned to control values by 12 days after the last dose. The DA levels in the striatum were increased 30 min after a single dose of cocaine. None of the other treatments elicited any changes in DA or 5-hydroxytryptamine or their metabolites. The subchronic cocaine administration to dopaminergic denervated rats with 6-hydroxydopamine failed to evoke any increase in DYN levels in the striatum or substantia nigra. The concurrent administration of the D1 DA antagonist, SCH-23390, or the D2 DA antagonist, spiperone, to the subchronic regimen of cocaine also blocked the cocaine-induced increase in DYN levels. These results indicate that cocaine selectively enhances the synthesis or decreases the release of DYN in the striatonigral neurons.(ABSTRACT TRUNCATED AT 250 WORDS)