上海精神医学
上海精神醫學
상해정신의학
SHANGHAI ARCHIVES OF PSYCHIATRY
2011年
4期
221-228
,共8页
李刚%纪蒙蒙%杨帅%崔东红%曹焕军%于剑锋
李剛%紀矇矇%楊帥%崔東紅%曹煥軍%于劍鋒
리강%기몽몽%양수%최동홍%조환군%우검봉
利培酮%氟哌啶醇%氯胺酮%精神分裂症%痛阈%运动行为%动物模型
利培酮%氟哌啶醇%氯胺酮%精神分裂癥%痛閾%運動行為%動物模型
리배동%불고정순%록알동%정신분렬증%통역%운동행위%동물모형
Risperidone%Haloperidol%Ketamine%Schizophrenia%Pain threshold%Motor behavior%Animal models
背景既往研究提示精神分裂症患者的疼痛敏感性降低并且可以被抗精神病药物部分逆转.对这一假说的评价方法之一是检测精神分裂症模型.目的在显示出预期的行为学改变的氯胺酮诱导的精神分裂症大鼠模型中,检测是否出现痛阈升高,并且检测抗精神病药物预处理是否逆转这种痛阈升高.方法将30只雄性Wistar大鼠随机分为5组,其中3组先腹腔注射抗精神病药物预处理[利培酮(0.3 mg/kg)、利培酮(0.9 mg/kg)或氟哌啶醇(1 mg/kg)],30 min后再腹腔注射氯胺酮(100 mg/kg);1组先腹腔注射生理盐水,再腹腔注射氯胺酮;1个对照组接受2次生理盐水注射.测定大鼠在基线以及第二次注射后第5、15、30和45 min的压痛和热痛阈值.另外的30只大鼠做同样处理,用旷场实验观测大鼠在第二次注射后120 min内的行为改变.结果 与对照组相比,在所有时间段内,氯胺酮组大鼠(未用抗精神病药物)出现压痛阈降低、热痛阈升高.在所有时间段内,氟哌啶醇预处理明显减轻了氯胺酮诱导的压痛降低,但高或低剂量的利培酮对压痛阈无明显影响.用低剂量利培酮预处理减轻了氯胺酮诱导的第5 min时段的热痛阈升高,但不包括第15~45 min时段.高剂量利培酮和氟哌啶醇对热痛阈无明显影响.在旷场实验中,抗精神病药物预处理的各组比仅用氯胺酮处理的一组有较少的直立行为(目标指向的行为),较少的穿越格子行为(较低的高运动性),较少的摇头和转圈运动.氟哌啶醇预处理组比氯胺酮组(无预处理)和2个利培酮预处理组相比,摔倒(即共济失调)更为常见.结论 我们不能肯定先前所见的在精神分裂症大鼠模型中抗精神病药物对氯胺酮诱导的痛阈升高有抑制作用.氯胺酮引起的压痛阈明显降低可能与氯胺酮注射后增强的全身活动性有关(这使压痛阈检测难以可靠进行).利培酮和氟哌啶醇有效减轻多方面的氯胺酮引起的拟精神病症状,而氟哌啶醇增强了氯胺酮引起的共济失调,利培酮降低了共济失调.这一资料与易于摔倒的老年患者有临床相关性.
揹景既往研究提示精神分裂癥患者的疼痛敏感性降低併且可以被抗精神病藥物部分逆轉.對這一假說的評價方法之一是檢測精神分裂癥模型.目的在顯示齣預期的行為學改變的氯胺酮誘導的精神分裂癥大鼠模型中,檢測是否齣現痛閾升高,併且檢測抗精神病藥物預處理是否逆轉這種痛閾升高.方法將30隻雄性Wistar大鼠隨機分為5組,其中3組先腹腔註射抗精神病藥物預處理[利培酮(0.3 mg/kg)、利培酮(0.9 mg/kg)或氟哌啶醇(1 mg/kg)],30 min後再腹腔註射氯胺酮(100 mg/kg);1組先腹腔註射生理鹽水,再腹腔註射氯胺酮;1箇對照組接受2次生理鹽水註射.測定大鼠在基線以及第二次註射後第5、15、30和45 min的壓痛和熱痛閾值.另外的30隻大鼠做同樣處理,用曠場實驗觀測大鼠在第二次註射後120 min內的行為改變.結果 與對照組相比,在所有時間段內,氯胺酮組大鼠(未用抗精神病藥物)齣現壓痛閾降低、熱痛閾升高.在所有時間段內,氟哌啶醇預處理明顯減輕瞭氯胺酮誘導的壓痛降低,但高或低劑量的利培酮對壓痛閾無明顯影響.用低劑量利培酮預處理減輕瞭氯胺酮誘導的第5 min時段的熱痛閾升高,但不包括第15~45 min時段.高劑量利培酮和氟哌啶醇對熱痛閾無明顯影響.在曠場實驗中,抗精神病藥物預處理的各組比僅用氯胺酮處理的一組有較少的直立行為(目標指嚮的行為),較少的穿越格子行為(較低的高運動性),較少的搖頭和轉圈運動.氟哌啶醇預處理組比氯胺酮組(無預處理)和2箇利培酮預處理組相比,摔倒(即共濟失調)更為常見.結論 我們不能肯定先前所見的在精神分裂癥大鼠模型中抗精神病藥物對氯胺酮誘導的痛閾升高有抑製作用.氯胺酮引起的壓痛閾明顯降低可能與氯胺酮註射後增彊的全身活動性有關(這使壓痛閾檢測難以可靠進行).利培酮和氟哌啶醇有效減輕多方麵的氯胺酮引起的擬精神病癥狀,而氟哌啶醇增彊瞭氯胺酮引起的共濟失調,利培酮降低瞭共濟失調.這一資料與易于摔倒的老年患者有臨床相關性.
배경기왕연구제시정신분렬증환자적동통민감성강저병차가이피항정신병약물부분역전.대저일가설적평개방법지일시검측정신분렬증모형.목적재현시출예기적행위학개변적록알동유도적정신분렬증대서모형중,검측시부출현통역승고,병차검측항정신병약물예처리시부역전저충통역승고.방법장30지웅성Wistar대서수궤분위5조,기중3조선복강주사항정신병약물예처리[리배동(0.3 mg/kg)、리배동(0.9 mg/kg)혹불고정순(1 mg/kg)],30 min후재복강주사록알동(100 mg/kg);1조선복강주사생리염수,재복강주사록알동;1개대조조접수2차생리염수주사.측정대서재기선이급제이차주사후제5、15、30화45 min적압통화열통역치.령외적30지대서주동양처리,용광장실험관측대서재제이차주사후120 min내적행위개변.결과 여대조조상비,재소유시간단내,록알동조대서(미용항정신병약물)출현압통역강저、열통역승고.재소유시간단내,불고정순예처리명현감경료록알동유도적압통강저,단고혹저제량적리배동대압통역무명현영향.용저제량리배동예처리감경료록알동유도적제5 min시단적열통역승고,단불포괄제15~45 min시단.고제량리배동화불고정순대열통역무명현영향.재광장실험중,항정신병약물예처리적각조비부용록알동처리적일조유교소적직립행위(목표지향적행위),교소적천월격자행위(교저적고운동성),교소적요두화전권운동.불고정순예처리조비록알동조(무예처리)화2개리배동예처리조상비,솔도(즉공제실조)경위상견.결론 아문불능긍정선전소견적재정신분렬증대서모형중항정신병약물대록알동유도적통역승고유억제작용.록알동인기적압통역명현강저가능여록알동주사후증강적전신활동성유관(저사압통역검측난이가고진행).리배동화불고정순유효감경다방면적록알동인기적의정신병증상,이불고정순증강료록알동인기적공제실조,리배동강저료공제실조.저일자료여역우솔도적노년환자유림상상관성.
Background:Previous investigations have suggested that patients with schizophrenia have decreased pain sensitivity that is partially reversed with antipsychotic treatment.One way to assess this hypothesis is to test it in animal models of schizophrenia.Objective: Determine whether or not rats that manifest the expected behavioral changes of a ketamine-induced rat model of schizophrenia have an increased pain threshold,and test whether or not pretreatment with antipsychotic medication reverses this increase in the pain threshold.Methods: 30 male Wistar rats were randomly assigned to five groups:three groups received intraperitoneal anti-pscyhotics [risperidone (0.3mg/kg),risperidone (0.9mg/kg) or haloperidol (1mg/kg)] 30 minutes prior to receiving intraperitoneal ketamine (100mg/kg);one group received normal saline followed by intraperitoneal ketamine;and a control group received two injections of normal saline.The threshold values for pressure pain and thermal pain were assessed at baseline and at 5,15,30 and 45 minutes after the second injection.The behaviors of another 30 rats treated in the same manner were assessed using the open field test for 120 minutes after receiving the second injection.Results: Compared to the control group,rats in the ketamine group (without pretreatment with antipsychotics) had decreased thresholds for pressure pain and increased thresholds for thermal pain at all time periods after administration of ketamine.Pretreatment with haloperidol significantly diminished the ketamine-induced decreased pressure pain threshold at all time periods but low-or high-dose risperidone had no effect on pressure pain thresholds.Pretreatment with low-dose risperidone reduced the ketamine-induced increase in thermal pain threshold 5 minutes after the ketamine injection but not at 15-45 minutes after the ketamine injection;high-dose risperidone and haloperidol had no significant effect on thermal pain thresholds.In the open field test the groups pretreated with antipsychotics had fewer standing upright behaviors (goal-directed behavior),fewer crossed grids (less hyperactivity),and fewer head shakes and circuling body movements (less stereotyped behavior) than the rats treated with ketamine that did not receive pretreatment with antipsychotics.Falls (i.e.,ataxia) were significantly more common in the haloperidol pretreatment group than in the ketamine group (without pretreatment) and than in the two risperidone pretreatment groups.Conclusion: We did not confirm previous findings about the inhibition of ketamine-induced increased pain thresholds by antipsychotics in a rat model of schizophrenia.The surprising decrease in pressure-pain thresholds with ketamine may be related to the increased overall activity following ketamine injection (which made it difficult to reliably conduct the pressure pain threshold test).Risperidone and haloperidol effectively reduce many of the psychomimetic effects of ketamine,but haloperidol increased ketamine-induced ataxia while risperidone decreased ataxia,a finding that could be clinically relevant for elderly patients who are prone to falls.
