多次应用氟西汀对苯环己哌啶诱导的青年大鼠自主运动增多行为的长期影响  

Adult Responsiveness to Fluoxetine Is Not Altered by Antidepressant Exposure in Adolescence in the Phencyclidine Induced Hyperlocomotion Model

作　　者：束庆[1] 严思敏 姚瑶[1] 葛卫红[1] 李鸣[2] SHU Qing;YAN Simin;YAO Yao;GE Weihong;LI Ming(Department of Pharmacy,Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing 210008,China;Department of Psychology,University of Nebraska-Lincoln,Lincoln,Nebraska 68588-0308,USA)

机构地区：[1]南京大学医学院附属鼓楼医院药学部,南京210008 [2]内布拉斯加州-林肯大学心理系,美国68588-0308

出　　处：《药学与临床研究》2019年第5期321-326,共6页Pharmaceutical and Clinical Research

基　　金：国家自然科学基金项目（81603087、81603102）;南京市医学科技发展资金项目（QRX17140）;江苏省药学会-奥赛康医院药学基金项目（A201704）;南京鼓楼医院新技术发展基金项目（XJSFZJJ201806）

摘　　要：目的:考察用苯环己哌啶(phencyclidine,PCP)建立的精神分裂症青年大鼠模型,在连续5天接受氟西汀(fluoxetine,FLX)后,对大鼠成年后再次暴露于FLX时对该药的长期反应的变化。方法:通过检测与精神分裂症相关的自主运动行为和考察感觉门控(sensorygating,SG)功能的前脉冲抑制(prepulseinhibition,PPI),来评价大鼠青年时期使用FLX是否会对其成年后的行为产生影响,以及FLX是否具有抗精神分裂症药物的活性作用。青年雄性SD大鼠(postnatalday,第40天)随机分为空白对照组(vehicle+vehicle)、PCP造模组(VEH+PCP)、FLX5.0mg·kg^-1给药组(FLX5+PCP)和FLX10.0mg·kg^-1给药组(FLX10+PCP)。从第42天起连续5天每天先接受分组药物处理,后在自主运动(locomotoractivity,LA)行为检测仪器中观察30min,再分别接受PCP或VEH的处理,继续进行60min的LA测试。在大鼠第47、66、77、94天时,所有大鼠进行PPI测试。成年时期(第76、91天),对所有大鼠再次给予FLX并检测90min(30min+60min)的LA行为。结果:(1)4组大鼠连续5天在给予VEH或FLX后的30min的平均LA次数统计显示:空白对照组大鼠的平均LA次数显著高于其他3个组(Ps<0.05)。而给予VEH或PCP后的60min的平均LA次数统计分析显示:空白对照组大鼠LA次数显著低于其他3个组(Ps<0.05),空白对照组大鼠LA次数与FLX给药组2组比较无统计学差异(Ps>0.05)。(2)大鼠成年后再次接受FLX处理,青年时期接受过FLX处理的2组大鼠的LA次数与模型组无统计学差异:第76天Ps>0.05;第91天Ps>0.05。(3)在大鼠青年、成年时即第47、66、77、94天时的PPI测试结果各组间均无统计学差异(Ps>0.05)。结论:青年大鼠经FLX(5.0mg·kg^-1或10.0mg·kg^-1)5天给药,未见抑制或增强PCP诱导的LA增多作用,大鼠成年后再次接触FLX时的LA行为未见统计学意义的改变及中枢的SG通道功能。即FLX在由PCP建立的大鼠LA行为增多模型中没有抗精神分裂症的药理作用。Objective: The present study investigated the persistence effect of fluoxetine from adolescence to adulthood in phencyclidine (PCP)-induced hyperlocomotion model. Methods: To assess how adolescent fluoxetine and PCP treatment affect the behavioral functions and developments of adolescent rats, we examined the prepulse inhibition (PPI) of acoustic startle response (ASR) periodically throughout their developmental period. Male adolescent Sprague-Dawley rats (P 44) were first treated with fluoxetine (FLX 5.0 or 10.0 mg·kg^-1) or vehicle and tested in the PCP (3.2 mg·kg-1)-induced hyperlocomotion model for 5 consecutive days. Then two tests with FLX (5.0 or 10.0 mg·kg^-1) were conducted after they matured into adults (P 76 and 91), respectively. A total of four separate PPI tests were conducted throughout the development period (P 47, P 66, P 77, P 94). Results: 1) FLX did not inhibit the PCP-induced hyperlocomotion during the adolescent period (Ps>0.05). 2) In the subsequent three FLX retreatment tests, the two FLX groups showed neither sensitization nor tolerance effects (P 76 Ps>0.05, P 91 Ps>0.05). 3) Repeated FLX and PCP treatment did not significantly impair the sensorimotor gating ability at the four points of testing (P 47 Ps>0.05, P 66 Ps>0.05, P 77 Ps>0.05, P 94 Ps>0.05). Conclusion: Adult responsiveness to fluoxetine is not altered by antidepressant exposure in adolescence in the PCP-induced hyperlocomotion model. FLX does not exhibit the property of antipsychotics in the PCP-induced hyperlocomotion model.

关 键 词：氟西汀 苯环己哌啶 青年时期 自主运动行为 前脉冲抑制 

分 类 号：R965[医药卫生—药理学]