研究中枢5-羟色胺能系统对吗啡诱导小鼠行为敏化的介导作用.选用雄性昆明小鼠,每天2次注射生理盐水或吗啡10mg/kg,连续3天.停药5天后,于第9天,进行吗啡激发试验,测定小鼠的自主活动60min,观察行为敏化效应.此外,选用5-羟色胺前体物质5-羟色氨酸作为工具药,分别在吗啡处理阶段(形成期),吗啡停药阶段(转换期)以及吗啡激发试验前腹腔注射20一80mg/kg5-羟色氨酸.激发试验给予吗啡后,立即测定小鼠的自主活动.实验第9天激发试验数据表明,每天2次反复给予吗啡的小鼠,其自主活动明显高于生理盐水对照组,说明小鼠对吗啡产生了行为敏化效应.5-羟色氨酸可以选择性抑制吗啡对小鼠行为敏化的诱导作用,其抑制作用呈剂量依赖性.然而,5-羟色氨酸对小鼠吗啡行为敏化的转换和表达无明显药理作用.因此,中枢5-羟色胺能系统的功能水平上调可能对吗啡诱导小鼠行为敏化效应具有一定的抑制作用.%To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice.Male Kunming mice were treated (i.p.) with saline or morphine 10 mg/kg twice daily for 3 d and then drug manipulafien was suspended for 5 d.On day 9,a challenge dose of morphine (10 mg/kg) was given and the locomotor activity was measured for 60 min to confirm the establishment of behavioral sensitization in mice.Moreover,5-hydroxytryptophan (5-HTP),a precursor of serotonin,at the doses of 20-80 mg/kg was given i.p.in combination with daily morphine treatment (induction),during the morphine treatment suspension (transfer) or prior to the challenge dose of morphine (expression) and locomotor activity was measured on day 9alter the challenge dose of morphine.Twice daily of morphine injection induced robust behavioral sensitization in mice as evidenced by significantly higher locomotion on day 9 for multiple treatment with morphine than saline in mice.5-HTP treatment selectively and dose-dependently blocked the induction,but not the transfer nor the expression of morphine induced behavioral sensitization.This study provides clear evidence that up-regulation of central serotonergic system may suppress the induction of morphine sensitization in mice.
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