急性脑卒中后焦虑抑郁共病状态血清单胺类递质的变化研究

目的探讨急性脑卒中后焦虑抑郁共病患者血清单胺类递质水平的关系。方法采用荧光分光光度计法测定33例急性卒中后焦虑抑郁共病患者、22例急性卒中后抑郁患者、49例卒中后非焦虑抑郁患者及37例正常人血清单胺类递质的水平。结果急性脑卒中后焦虑抑郁共病组和PSD组血清中，NE、5-HT、DA含量低于非焦虑抑郁组和对照组，共病组NE、5-HT高于抑郁组，其中5-HT差异有显著意义，而非焦虑抑郁组血清中，单胺类递质的含量亦低于对照组。而大脑左侧及前部卒中患者的血清中单胺类递质水平低于其它卒中部位患者（P〈0．05）。结论急性脑卒中后焦虑抑郁共病组和单纯PSD的发生与血清中单胺类神经递质的降低有关。     

蒙医针刺对卒中后抑郁模型大鼠的影响

目的观察蒙医针刺对卒中后抑郁(PSD)模型大鼠的影响。方法把24只SD雄性大鼠随机分为假手术组、模型组、针刺组、西药组,自由饲养。应用栓线法形成局灶性脑缺血再灌注损伤后实施慢性温和性应激刺激结合孤养14d,建立PSD模型。模型成立后治疗14d。酶联免疫法(ELISA)检测大鼠海马组织的5-HT、NE、DA含量和血清IL-2、IL-6、TNF-α表达。结果治疗后,与假手术组比较,模型组大鼠海马组织的5-HT、NE、DA含量显著降低(P0.01,P0.05);血清IL-2、IL-6和TNF-α表达水平显著增高(P0.01)。与模型组大鼠比较,针刺组和西药组大鼠海马组织5-HT、NE、DA含量显著增加(P0.01,P0.05);血清IL-2、IL-6和TNF-α表达水平显著降低(P0.01,P0.05)。针刺组与西药组无显著性差异(P0.05)。结论蒙医针刺可明显增加脑组织的单胺递质含量,调节血清细胞因子水平,说明蒙医针刺治疗卒中后抑郁症有一定的抗抑郁作用。     

雌激素对脑卒中后抑郁大鼠抑郁行为学及前额叶BDNF表达的影响

目的:探讨雌激素对脑卒中后抑郁(PSD)大鼠的影响及分子机制.方法:应用大脑中动脉栓塞和慢性不可预见温和刺激方法制备大鼠PSD模型.将PSD大鼠分为雌激素组(PSD大鼠皮下注射雌二醇),PSD组(PSD大鼠皮下注射大豆油)和对照组(假手术,皮下注射大豆油).3组的不同干预均持续14 d.观察各组大鼠行为学和前额叶脑源性生长因子(BDNF)的含量改变.结果:雌激素组在雌二醇干预后强迫游泳测试结果表明行为学显著改善:不动时间减少,与PSD组比较(18.4±4.84 vs 52.1±5.38)差异有显著统计学意义(P<0.01),雌激素组挣扎时间增加,与PSD组比较(63.8±12.31 vs 36.3±5.22)差异有统计学意义(P<0.05).前额叶BDNF含量在雌激素组也显著增高:雌激素组与PSD组比较,P<0.05;PSD组与对照组比较,P<0.01.结论:雌激素可能通过BDNF通路改善PSD大鼠的抑郁症状.     

盐酸帕罗西汀对脑卒中后束缚应激大鼠行为学和下丘脑内单胺递质的影响

目的:探讨盐酸帕罗西汀对脑卒中后束缚应激大鼠脑内单胺递质的影响.方法:建立脑卒中后束缚应激大鼠模型,观察各组大鼠糖水消耗试验、自发性行为改变和下丘脑单胺类神经递质的变化.结果:模型组大鼠蔗糖水饮用量、旷野实验水平及垂直得分、下丘脑NE、5-HT、DA含量等与正常组相比明显减少;帕罗西汀组大鼠糖水饮用量、旷野实验中的得分和下丘脑神经递质的含量较模型组大鼠明显增加.结论:盐酸帕罗西汀对脑卒中后束缚应激大鼠模型的作用可能与增加下丘脑单胺类神经递质的含量有关.     

香兰素吸嗅对大鼠抑郁样行为及脑单胺类神经递质的影响

目的研究香兰素吸嗅对大鼠抑郁样行为改善及其机制。方法慢性不可预见性中等强度应激(CUMS)+孤养的方法建立大鼠抑郁症模型。为验证香兰素作用途径,另设立大鼠嗅球毁损(OBX)模型。于造模前、后及干预后4 w测试大鼠糖水消耗量和强迫游泳不动时间,干预结束后超高压液相色谱检测大鼠脑内5-HT、DA、NE的量。结果与造模后相比,CUMS+香兰素吸嗅组大鼠神经行为学指标显著好转(P<0.05);其脑匀浆液5-HT、DA的量显著高于空白对照组(P<0.05)。与造模后相比OBX+香兰素吸嗅组大鼠神经行为学指标未见好转(P>0.05);其脑匀浆液5-HT、DA、NE均显著低于假手术组(P<0.05)。结论香兰素可经嗅觉通路改善大鼠抑郁样行为,其机制可能通过提升脑内5-HT、DA实现的。     

脑卒中后抑郁大鼠海马齿状回5-羟色胺1A受体的表达

目的 观察脑卒中后抑郁(PSD)大鼠海马齿状回5-羟色胺1A(5-HT1A)受体的表达.方法 将SD雄性大鼠分为正常对照组、卒中组、应激抑郁对照组和PSD组,每组6只.应用左侧大脑中动脉阻塞(MCAO)联合不可预见的慢性温和应激(CMS)刺激及孤养法建立PSD大鼠模型,采用荧光实时定量聚合酶链反应和Western印迹法检测并比较各组大鼠CMS第19天和第28天齿状回5-HT1A受体(mRNA)和蛋白表达水平.结果 (1)CMS第19天,PSD组5-HT1A受体mRNA表达(O.012±0.001)低于正常对照组(0.361±0.010)和卒中组(0.039±0.002;P＜0.001);其5-HT1A受体蛋白表达(0.400±0.030)低于正常组(1.320±0.060)和卒中组(0.610±0.060;均P＜0.001).(2)CMS第28天,PSD组5-HT1A受体mRNA(0.013±0.001)低于正常对照组(0.336±0.011)、卒中组(0.063±0.006;均P＜0.001);其5-HT1A受体蛋白表达(0.080±0.020)低于正常组(0.620 ±0.030)、卒中组(0.260±0.040)和应激抑郁组(0.320±0.020;均P＜0.001).结论 PsD大鼠海马齿状回5-HT1A受体表达水平降低,此改变可能是PSD发病的分子机制之一.     

氟西汀对卒中后抑郁大鼠海马脑源性神经营养因子表达的影响

目的 分析卒中后抑郁（post-stroke depression，PSD）模型大鼠海马脑源性神经营养因子（Brainderived neurotrophic factor，BDNF）蛋白及mRNA表达水平，及抗抑郁剂氟西汀干预后BDNF表达水平的变化，初步探讨BDNF在PSD发生中的作用。方法 大脑中动脉阻塞（Middle cerebral artery occlusion，MCAO）法建立局灶脑缺血模型，加用慢性不可预见温和应激（Chronic unpredictable mild stress，CUMS）结合孤养，建立PSD大鼠模型，并予以氟西汀干预。应用蛋白免疫印迹（Western-blot）、Real time-PCR分别检测应激18、28 d时海马BDNF蛋白及mRNA表达水平。结果 与对照组相比，应激14d后PSD组较对照组大鼠体重与糖水消耗比例降低，水平、垂直试验得分下降（P <0.05或P <0.01）。氟西汀干预组糖水消耗比例，水平、垂直试验得分均较PSD组显著增加（P <0.05或P <0.01）。第18、28天，PSD组BDNF蛋白水平较对照组均显著下降（P <0.05或P <0.01）。PSD组BDNF mRNA的表达在应激18d时较正常组有下降趋势，但无统计学意义；至28 d时，表达含量明显下降，差异有统计学意义（P <0.01）。第18、28天，氟西汀干预组BDNF蛋白及mRNA水平均较PSD组显著增加（P <0.01）。结论 应用MCAO模型联合CUMS加孤养模型制备的PSD大鼠模型在神经功能缺损的同时，表现快感缺乏和探索行为减少的抑郁核心症状，并且体重的增长幅度显著减慢。PSD大鼠海马BDNF蛋白及mRNA表达水平显著降低，氟西汀干预后BDNF表达水平上升，初步提示BDNF在卒中后抑郁发生中的作用。     

草酸艾司西酞普兰联合黛力新对脑卒中后抑郁障碍患者的疗效及对血清指标的影响

目的探讨草酸艾司西酞普兰联合黛力新对脑卒中后抑郁障碍(PSD)的疗效及对一些血清指标的影响。方法将92例PSD患者随机分为两组:观察组(n=46)应用草酸艾司西酞普兰联合黛力新治疗,对照组(n=46)应用黛力新治疗。治疗前后评估美国国立卫生研究院卒中量表(NIHSS)、日常生活活动能力Barthel指数(BI)、汉密尔顿抑郁量表(HAMD)和简易智力状态检查量表(MMSE)评分,测定血清5-羟色胺(5-HT)、多巴胺(DA)、去甲肾上腺素(NE)、神经生长因子(NGF)和脑源性神经营养因子(BDNF)水平。结果治疗前两组患者的上述指标结果,组间无明显差异(P0.05);治疗后观察组的NIHSS、HAMD评分显著低于对照组,BI、MMSE评分显著高于对照组(P0.05);治疗后观察组血清5-HT、NGF和BDNF水平均显著高于对照组(P0.05),两组血清NE、DA无明显差异(P0.05)。结论草酸艾司西酞普兰联合黛力新治疗PSD能够促进保护性神经递质与神经细胞因子的合成与释放,有效减轻抑郁状态,促进神经功能和认知功能的改善。     

西酞普兰对脑卒中后抑郁大鼠海马齿状回5-羟色胺1A受体表达的影响

目的 观察西酞普兰对拟脑卒中后抑郁(post-stroke depression,PSD)大鼠海马齿状回5-羟色胺1A(5-HT1A)受体表达的影响,探讨其治疗PSD可能的药理机制.方法 将雄性SD大鼠分为3组正常对照组、拟PSD组和西酞普兰干预组.左侧大脑中动脉阻塞(MCAO)联合慢性不可预见温和应激刺激(CMS)及孤养法建立拟PSD动物模型,同时予西酞普兰(10 mg·kg-1·day-1)干预4周,荧光实时定量PCR和Western印迹方法检测并比较CMS开始后第19、28天各组大鼠海马齿状回5-HT1A受体的基因(mRNA表达水平)和蛋白表达水平.结果 CMS开始后第19天,西酞普兰组5-HT1A受体的基因和蛋白表达均高于拟PSD组[(0.131±0.008)vs(0.012±0.001)和(0.95±0.06)vs(0.40±0.03),P均小于0.001].第28天,西酞普兰组5-HT1A受体的基因和蛋白表达均高于拟PSD组[(0.224±0.012)vs(0.013±0.001)和(0.52±0.06)vs(0.08±0.02),P均小于0.001].结论 西酞普兰促进拟PSD大鼠海马齿状回5-HT1A受体的基因和蛋白表达,从而可促进海马神经重塑,这可能为西酞普兰治疗PSD的分子机制之一.     

卡左双多巴控释片联合多巴丝肼片对帕金森患者认知功能与血清因子水平的影响

目的观察帕金森患者应用卡左双多巴控释片联合多巴丝肼片治疗后的疗效及认知功能变化。方法将我院97例帕金森患者采用随机数字表法分组,对照组48例给予多巴丝肼片口服,观察组49例联合卡左双多巴控释片口服,对比两组患者治疗后认知功能、精神状态、多巴胺(DA)、去甲肾上腺素(NE)、5-羟色胺(5-HT)、血清脑源性神经营养因子(BDNF)水平变化、临床疗效及不良事件发生率。结果观察组治疗后5-HT、BDNF、NE、DA水平、MoCA、MMSE评分及总有效率均高于对照组,UPDRES评分低于对照组(P0.05);不良事件发生率低于对照组(P0.05)。结论卡左双多巴控释片联合多巴丝肼片有效改善帕金森患者认知功能及精神状态,其机制可能与提升多巴胺水平,调节5-HT、BDNF、NE水平有关。     

Chronic variable stress and partial 5-HT denervation by parachloroamphetamine treatment in the rat: effects on behavior and monoamine neurochemistry

Chronic variable stress (CVS) and manipulations of 5-HT-ergic neurotransmission are increasingly used as animal models of depression. In the present study, CVS for 2 weeks and a partial lesion of 5-HT projections by a small dose of parachloroamphetamine (PCA, 2 mg/kg) were applied independently or in combination. CVS reduced significantly the gain in body weight and increased the number of defecations in the open field test. PCA reduced body weight only within the first 24 h after its administration. Consumption of sucrose solution and its preference to water in non-deprived rats were significantly higher in PCA-pretreated rats 2 weeks after CVS compared to control animals. In the forced swimming test, both PCA and CVS treatments reduced immobility on the first but not the second session. Both treatments reduced significantly the time rats spent in social interaction. CVS also elicited an increase in the weight of the right adrenal, but this effect was not present in the PCA-pretreated group. PCA reduced 5-HT and 5-HIAA levels in the frontal cortex, hippocampus, and septum by approximately 20%. CVS increased HVA levels in the frontal cortex. Applied together, PCA pretreatment and CVS increased dopamine turnover in the frontal cortex. Conclusively, this study has provided evidence that chronic variable stress, which elicited expected physiological and neurochemical changes, does not reduce sucrose intake or preference in non-deprived animals, but, instead, may increase it after partial 5-HT-ergic denervation; and that partial 5-HT-ergic denervation by a low dose PCA treatment has a long-lasting effect on forced swimming and social behavior similar to chronic stress.     

Effects of neonatal rat Borna disease virus (BDV) infection on the postnatal development of the brain monoaminergic systems

Effects of neonatal Borna disease virus infection (BDV) on the postnatal development of brain monoaminergic systems in rats were studied. Tissue content of norepinephrine (NE), dopamine (DA) and its metabolite, 3,4-dihydroxyphenol acetic acid (DOPAC), and serotonin (5-HT) and its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed by means of HPLC-EC in frontal cortex, cerebellum, hippocampus, hypothalamus and striatum of neonatally BDV-infected and sham-inoculated male Lewis rats of 8, 14, 21, 60 and 90 days of age. Both NE and 5-HT concentrations were significantly affected by neonatal BDV infection. The cortical and cerebellar levels of NE and 5-HT were significantly greater in BDV-infected rats than control animals at postnatal days (PND) 60 and 90. Tissue content of NE in hippocampus was unaffected. In hippocampus, neonatally BDV-infected rats had lower 5-HT levels at PND 8 and significantly elevated levels at PND 21 and onwards. Neither striatal levels of 5-HT nor hypothalamic levels of 5-HT and NE were affected by neonatal BDV infection, suggesting that the monoamine systems in the prenatally maturing brain regions are less sensitive to effects of neonatal viral infection. 5-HIAA/5-HT ratio was not altered in BDV-infected rats indicating no changes in the 5-HT turnover in the brain regions damaged by the virus. Neither DA nor DOPAC/DA ratio was affected by neonatal BDV infection in any of the brain regions examined. The present data demonstrate significant and specific alterations in monoaminergic systems in neonatally BDV-infected rats. This pattern of changes is consistent with the previously reported behavioral abnormalities resulting from neonatal BDV infection.     

慢性应激诱导的抑郁大鼠海马脑源性神经营养因子蛋白和miR-16的表达

目的 研究慢性应激对大鼠行为及海马中脑源性神经营养因子（BDNF）和microRNA-16（miR-16）表达的影响.方法 在大鼠出生后1d,按窝别分为慢性应激组和对照组,各6只.慢性应激组大鼠在其出生后第1-14天每天接受6h母爱剥夺应激,然后喂养至10周龄时给予21d慢性温和应激,对照组不给予任何处理.两组大鼠均于13周龄时,采用强迫游泳、糖水偏爱和旷场试验测定大鼠的行为,采用免疫印迹法检测BDNF蛋白的表达情况,采用实时定量聚合酶链反应检测海马miR-16表达水平.结果 旷场实验中,应激组大鼠直立次数少于对照组（P＜0.05）,而爬行总路程,中央格比例和大便颗数差异均无统计学意义（P＞0.05）;强迫游泳实验中应激组大鼠的被动漂浮时间长于对照组（P＜0.05）;糖水测验中应激组大鼠的糖水偏爱率低于对照组（P＜0.05）.应激组大鼠海马BDNF蛋白表达量低于对照组（P＜0.05）;应激组大鼠海马内miR-16的表达量高于对照组（P＜0.05）.Pearson相关分析显示,两组大鼠的miR-16表达水平均与BDNF蛋白表达水平呈负相关（P＜0.05）.大鼠直立次数和糖水偏爱率分别与海马内BDNF蛋白表达量与呈正相关（P＜0.05）,与miR-16表达量呈负相关（P＜0.05）而被动漂浮时间与海马内BDNF蛋白表达量呈负相关（P＜0.05）,与miR-16表达量呈正相关（P＜0.05）.结论 慢性应激可导致大鼠抑郁样行为的出现及海马中miR-16与BDNF蛋白表达发生改变,并且大鼠的抑郁样水平与海马中miR-16和BDNF蛋白表达水平明显相关;大鼠海马中miR-16与BDNF蛋白可能参与了调节抑郁症的病理过程.     

Prenatal 3,4-methylenedioxymethamphetamine (ecstasy) exposure induces long-term alterations in the dopaminergic and serotonergic functions in the rat

We investigated several aspects of the dopaminergic and serotonergic functions throughout brain development in rats prenatally exposed to MDMA ("ecstasy"). Pregnant rats were treated with MDMA (10 mg/kg s.c.) or saline from the 13th to the 20th day of gestation and studies were conducted on the progeny from both groups: (i) quantification of whole brain contents of DA, 5-HT and metabolites from the 14th day of embryonic life (E14) to weaning (21st day of postnatal life, P21); (ii) quantification of DA and 5-HT membrane transporters by autoradiography from E18 to adult age (P70); (iii) measurement of pharmacologically induced release of DA and 5-HT using microdialysis on adult (P70) freely moving rats; (iv) measurement of sucrose preference in adults (P70). Prenatally MDMA-exposed rats showed (i) a two-fold decrease of whole brain levels of 5-HT and 5-HIAA at P0; (ii) no effect on the DAT and SERT density; (iii) a strongly reduced pharmacologically induced release of DA and 5-HT at P70 in the striatum and hippocampus; and (iv) a significant 20% decrease in sucrose preference at P70. This study suggests that a prenatal exposure to MDMA induces transient and long-term neurochemical and behavioural modifications in dopaminergic and serotonergic functions.     

Relationship between parameters of serotonin transport and antidepressant plasma levels or therapeutic response in depressive patients treated with paroxetine and amitriptyline.

In a double-blind clinical study, antidepressant plasma levels, parameters of platelet serotonin (5-HT) transport (Km, Vmax and basal platelet 5-HT content) and therapeutic response were measured in depressive patients treated with either paroxetine (30 mg/day) or amitriptyline (150 mg/day) for 6 weeks. No correlation could be found between paroxetine plasma levels and therapeutic outcome after 2, 4 and 6 weeks of treatment. In contrast to the amitriptyline group, a marked increase in Km from baseline to week 2 was determined in paroxetine-treated patients, with Km increase being correlated with paroxetine plasma levels at week 2. However, no significant relationship could be found between 5-HT transport parameters and any of the outcome measures in either treatment group.     

Brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis adaptation processes in a depressive-like state induced by chronic restraint stress

Depression is potentially life-threatening. The most important neuroendocrine abnormality in this disorder is hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. Recent findings suggest that all depression treatments may boost the neurotrophin production especially brain-derived neurotrophic factor (BDNF). Moreover, BDNF is highly involved in the regulation of HPA axis activity. The aim of this study was to determine the impact of chronic stress (restraint 3 h/day for 3 weeks) on animal behavior and HPA axis activity in parallel with hippocampus, hypothalamus and pituitary BDNF levels. Chronic stress induced changes in anxiety (light/dark box test) and anhedonic states (sucrose preference test) and in depressive-like behavior (forced swimming test); general locomotor activity and body temperature were modified and animal body weight gain was reduced by 17%. HPA axis activity was highly modified by chronic stress, since basal levels of mRNA and peptide hypothalamic contents in CRH and AVP and plasma concentrations in ACTH and corticosterone were significantly increased. The HPA axis response to novel acute stress was also modified in chronically stressed rats, suggesting adaptive mechanisms. Basal BDNF contents were increased in the hippocampus, hypothalamus and pituitary in chronically stressed rats and the BDNF response to novel acute stress was also modified. This multiparametric study showed that chronic restraint stress induced a depressive-like state that was sustained by mechanisms associated with BDNF regulation.     

Dietary restriction changes behaviours in brain-derived neurotrophic factor heterozygous mice: role of serotonergic system

Accumulating evidence has suggested that brain-derived neurotrophic factor (BDNF) plays a role in eating behaviours, and that BDNF-heterozygous (+/-) mice exhibit abnormal behaviours (e.g. obesity, anxiety and aggression). The present study was undertaken to determine whether or not dietary restriction (DR) alters the behaviours in BDNF(+/-) mice, as DR has been shown to exert a number of beneficial effects on the brain. Eight-week-old male wild-type (+/+) and BDNF(+/-) mice were divided into two groups, ad libitum (AL) diet group and DR group, for 16 weeks. After carrying out a behavioural evaluation, we determined the BDNF mRNA levels, as well as mRNA levels for subtypes (5-HT(1A), 5-HT(1B), 5-HT(2A) and 5-HT(2C)) of the 5-HT receptor and 5-HT transporter (5-HTT), protein levels of BDNF and concentrations of 5-HT and 5-HIAA in the hypothalamus, hippocampus and frontal cortex. DR significantly ameliorated behaviours including obesity, anxiety and aggression in BDNF(+/-) mice. The concentrations of 5-HT and 5-HIAA in the frontal cortex, and 5-HT in the hippocampus, of BDNF(+/-) mice were significantly lower than those of wild-type mice. Interestingly, DR significantly increased the levels of 5-HT and 5-HIAA in the frontal cortex of BDNF(+/-) mice. These findings suggest that DR may alter the behaviours in BDNF(+/-) mice, and that the 5-HT system may be implicated in the beneficial effects of DR on these behaviours.     

Effect of corticotropin releasing factor receptor 1 antagonist on extracellular norepinephrine, dopamine and serotonin in hippocampus and prefrontal cortex of rats in vivo

Corticotropin releasing factor (CRF) is a major mediator of adaptive responsiveness to stress. We measured changes in extracellular concentrations of catecholamine and indoleamines in freely moving rats in response to administration of CRF1 antagonist CP-154,526 by using in vivo microdialysis. Dialysis probes were placed stereotaxically in either the hippocampus or the prefrontal cortex. We examined the response in the hippocampus or the prefrontal cortex to 32.0 mg/kg i.p. administration of CP-154,526. CP-154,526 reduced the extracellular concentration of norepinephrine (NE) from 30 min to 180 min and 5-hydroxytryptamine (5-HT) from 30 min to 60 min after injection in the hippocampus. CP-154,526 did not remarkably change dopamine (DA). There were no significant differences between CP-154,526 and vehicle in NE, 5-HT and DA in the prefrontal cortex. The present results indicate that CRF1 receptor antagonist produced a decrease in dialysate concentration of NE and 5-HT, but not DA, in the hippocampus. These results suggest that the CRH-1 receptor antagonist suppresses the release of NE and 5-HT in the hippocampus.     

Effects of ketamine on dopamine metabolism during anesthesia in discrete brain regions in mice: comparison with the effects during the recovery and subanesthetic phases

The effects of ketamine on the levels of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT, serotonin) and their metabolites were examined in discrete brain regions in mice. A high dose of ketamine (150 mg/kg, i.p.) did not change DA metabolism in the frontal cortex, nucleus accumbens, striatum and hippocampus, but did decrease it in the brainstem during anesthesia. In contrast, during recovery from the ketamine anesthesia, the high dose increased the level of homovanillic acid (HVA) in all brain regions. A low subanesthetic dose of ketamine (30 mg/kg, i.p.) increased the concentrations of both 3,4-dihydroxyphenylacetic acid (DOPAC) and HVA only in the nucleus accumbens. The DA level was not affected by any ketamine treatment. During ketamine anesthesia, the content of 3-methoxy-4-hydroxy-phenylglycol (MHPG) was decreased in the brainstem, whereas during recovery from anesthesia, the MHPG level was increased in the frontal cortex, nucleus accumbens and brainstem. The NE content was not altered in any region by ketamine treatment. The concentration of 5-hydroxyindoleacetic acid (5-HIAA) was reduced in the frontal cortex, striatum, hippocampus and brainstem during ketamine anesthesia. The 5-HT level was unaltered in all regions except the brainstem where it was reduced. In contrast, after anesthesia, the concentrations of both 5-HT and 5-HIAA were increased in the striatum. During the subanesthetic phase, however, the levels of NE, 5-HT and their metabolites were unchanged. These neurochemical results are consistent with the electrophysiological findings that a high dose of ketamine does not change the basal firing rates of nigrostriatal DA neurons during anesthesia, while low subanesthetic doses significantly increase those of ventral tegmental DA neurons.