重复注射烟碱诱发大鼠惊厥耐受形成的时间与剂量依赖性

Time- and dose-dependent tolerance to convulsions induced by repeated nicotine in rats

本研究的目的在于观察烟碱诱发大鼠惊厥耐受形成的特点．烟碱急性给药（２．０，３．５和５．０ｍｇ·ｋｇ－１ｓｃ）产生的惊厥具有剂量依赖性；美加明可完全对抗，但六甲溴胺不能使之缓解．烟碱（２．０，３．５和５．０ｍｇ·ｋｇ－１）连续１２ｄｓｃ后，ｄ１３给予一较小剂量（１．８ｍｇ·ｋｇ－１ｓｃ）激发，可观察到由于激发给药使耐受进一步形成．在激发给药１５ｍｉｎ后，取大鼠血及几个脑区组织，测定血清及脑组织匀浆中烟碱含量，实验显示各脑区烟碱含量也具有剂量依赖性，而血清烟碱维持在相同水平．这些结果表明：烟碱连续给药后诱发大鼠惊厥耐受性可在较早的几天内迅速产生，且与脑组织烟碱水平密切相关．

The purpose of this study was to examine the tolerance development of nicotine-induced convulsions in rats. Acute sc administrations of nicotine (2.0, 3.5 and 5.0 mg·kg -1 ) produced convulsions in a dose-dependent manner. Mecamylamine antagonized the convulsions, but hexamethonium did not modify it. Daily nicotine administrations (2.0, 3.5 and 5.0 mg·kg -1 ) for 12 d, the effect of a challenge administration of nicotine (1.8 mg·kg -1 ) on nicotine-induced convulsions were tested on d13. Further tolerance was also developed by the d13 challenge administration. After the d13 test, nicotine levels of the brain and blood 15 min after the challenge injection were measured, it showed that nicotine levels of several brain regions (cortex, cerebellum, hypothalamus, hippocampus and striatum) were increased in a dose-dependent manner. But a similar challenge injection had no effect on blood nicotine levels. These results indicated that the tolerance development of nicotine-induced convulsions appeared relatively earlier by daily nicotine administrations to rats, and was closely related to the increased nicotine level in the brain.