Effect of intracerebroventricular or intrathecal injection of NCS-382 on hypnosis and analgesia action of sevoflurane

OBJECTIVE To investigate the relationship between gamma-hydroxybutyric acid(GHB) receptors and hypnotic and analgesic effects of sevoflurane.METHODS ① Hypnosis experiment: after mice were ip given sevoflurane 5.5 ml·kg-1 to get hypnotized,NCS-382 0.05,0.25 and 1.25 mg·kg-1 were given intracerebroventricularly(icv) and sleeping time(ST) was observed.② Analgesia experiment: mice in normal saline and sevoflurane 2.0 ml·kg-1 groups were ith given artificial cerebral spinal fluid(aCSF),and NCS-382 0.05,0.25 and 1.25 mg·kg-1 as subgrouping,respectively.The pain threshold in hot-plate pain test(HPPT) was observed.③ Writhing test: mice in normal saline and sevoflurane 5.5 ml·kg-1(sc) groups were given aCSF,and NCS-382 0.05,0.25 and 1.25 mg·kg-1(ith) as subgrouping,respectively.The writhing times were observed.RESULTS After mice were hypnotized by sevoflurane,icv NCS-382 0.05,0.25 and 1.25 mg·kg-1could significantly shorten ST in mice treated with sevoflurane compared with aCSF by 50,52 and 78 min(P0.01).In hot-plate test,NCS-382 did not affect HPPT in conscious mice(P0.05),but could significantly decrease HPPT in mice treated with sevoflurane by 4.4,5.7 and 4.4 s(P0.01) respectively.Sevoflurane(sc) could significantly lead to a 14-fold decrease of writhing times(P0.01),but NCS-382 couldn′t(P0.05).CONCLUSIONGHB may be one of the important targets for hypnotic effects and analgesic effects on thermal-induced nociception,but have no correlation with chemical-induced or inflammation-induced nociception of sevoflurane.