茯苓总三萜抗惊厥作用的实验研究1)

目的 观察茯苓总三萜(TTP)对小鼠最大电休克模型、戊四唑模型以及大鼠皮层定位注射青霉素诱发癫痫模型的对抗作用.方法 采用最大电休克和戊四唑惊厥模型,灌胃小鼠不同剂量茯苓总三萜,以拉莫三嗪(LTG)为对照,观察其抗惊厥作用;建立大鼠皮层定位注射青霉素诱发癫痫模型,以拉莫三嗪为阳性对照,观察两种剂量茯苓总三萜灌胃给药对青霉素诱发癫痫发作和海马区痫性放电的潜伏期、痫波发放频率及痫波最高波幅的影响.结果 不同剂量TTP对MES模型均有对抗作用,且量效呈正相关性,但最大效能较拉莫三嗪弱.两种剂量TTP(80 mg/kg ,160 mg/kg)均可延长MET发作潜伏期,与对照组比较均有统计学意义(P<0.01),且作用较拉莫三嗪强.两种剂量茯苓总三萜(140 mg/kg ,280 mg/kg)和拉莫三嗪(180 mg/kg)均可延长大鼠癫痫发作潜伏期,减轻发作的程度,延长痫性放电的潜伏期(P<0.01),减少痫波发放频率,减小放电最高波幅,与模型组比较,均有统计学意义(P<0.05).结论 茯苓总三萜可明显对抗小鼠最大电休克和戊四唑惊厥,抑制大鼠皮层定位注射青霉素诱发的癫痫发作和痫性放电, 产生抗癫痫作用,但抗MES作用较拉莫三嗪弱而抗MET和青霉素惊厥作用较拉莫三嗪强.     

W_(112)抗癫痫作用量效-时效关系

目的验证W_(112)的抗癫痫活性。方法制备小鼠、大鼠最大电休克发作(MES)癫痫模型,观察W_(112)单体化合物灌胃给药抗癫痫作用的量效-时效关系。结果一次灌胃给药W_(112)单体化合物混悬液,小鼠于药后10 min、大鼠于药后30 min即具有明显的抗电惊厥作用,并分别可持续作用3 h和12 h以上,且均具有一定的剂量依赖性关系。结论 W_(112)具有明显的抗癫痫作用,是一种具有良好开发前景的抗癫痫新药。     

茯芩总三萜抗惊厥作用的实验研究

目的观察茯苓总三萜（TTP）对小鼠最大电休克模型、戊四唑模型以及大鼠皮层定位注射青霉素诱发癫痫模型的对抗作用。方法采用最大电休克和戊四唑惊厥模型,灌胃小鼠不同剂量茯苓总三萜,以拉莫三嗪（LTG）为对照,观察其抗惊厥作用;建立大鼠皮层定位注射青霉素诱发癫痫模型,以拉莫三嗪为阳性对照,观察两种剂量茯苓总三萜灌胃给药对青霉素诱发癫痫发作和海马区痫性放电的潜伏期、痫波发放频率及痫波最高波幅的影响。结果不同剂量TTP对MES模型均有对抗作用,且量效呈正相关性．但最大效能较拉莫三嗪弱。两种剂量TTP（80mg/kg．160mg／kg）均可延长MET发作潜伏期,与对照组比较均有统计学意义（P〈0．01）,且作用较拉莫三嗪强。两种剂量茯苓总三萜（140mg／kg,280mg／kg）和拉莫三唾（180mg／kg）均可延长大鼠癫痫发作潜伏觏减轻发作的程度．延长痫性放电的潜伏期（P〈0．01）,减少痫波发放频率,减小放电最高波幅,与模型组比较,均有统计学意义（P〈0．05）。结论茯苓总三萜可明显对抗小鼠最大电休克和戊四唑惊厥,抑制大鼠皮层定位注射青霉素诱发的癫痫发作和痫性放电。产生抗癫痫作用,但抗MES作用较拉莫三嗪弱而抗MET和青霉素惊厥作用较拉莫三嗪强。     

细叶远志皂苷对APP/PS1双转基因小鼠海马神经元及线粒体功能保护作用研究

目的 探讨细叶远志皂苷对APP/PS1双转基因小鼠海马神经元和线粒体功能保护作用.方法 将4月龄雄性APP/PS1双转基因小鼠40只分为模型组、低、中、高剂量组(细叶远志皂苷20 mg/kg、40 mg/kg,80 mg/kg灌胃,1次/d),每组10只,连续给药90 d,另选取4月龄雄性野生型小鼠15只作为正常对照组...     

人参皂苷Re、灯盏花素组合物对血管性痴呆大鼠的神经保护作用

目的 探讨人参皂苷Re、灯盏花素组合物对血管性痴呆(VD)大鼠的神经保护作用。方法 将64只大鼠随机分为假手术组、模型组、阳性药组(42 mg/kg血塞通胶囊)、组合物低剂量组(人参皂苷Re 2.5 mg/kg+灯盏花素1 mg/kg)、组合物中剂量组(人参皂苷Re 5.0 mg/kg+灯盏花素2 mg/kg)、组合物高剂量组(人参皂苷Re 10.0 mg/kg+灯盏花素4 mg/kg)、人参皂苷Re组(10 mg/kg)、灯盏花素组(4 mg/kg),每组8只。除假手术组外，各组采用双侧颈总动脉永久结扎法制作VD模型。造模后，假手术组和模型组给予等体积的纯净水灌胃，其余各组灌胃给药，每日1次，连续28 d。给予药物后，大鼠的学习及记忆能力应用Morris水迷宫检测，大鼠的海马组织中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6和IL-1β水平用酶联免疫吸附试验(ELISA)测定，组织病理用苏木素-伊红(HE)染色，观察海马区组织病理学改变。结果 模型组逃避潜伏期比假手术组显著延长(P<0.001)。与模型组比较，阳性药组从第2天开始，逃避潜伏期显著缩短(P<0.01)...     

W_(112)抗小鼠癫痫作用机制

目的探讨W_(112)的抗小鼠癫痫作用机制。方法采用戊四唑、3-巯基丙酸、荷包牡丹碱、硫代氨基脲诱发小鼠惊厥模型,灌胃给予小鼠W_(112)混悬液,观察4种化学物质诱发惊厥小鼠的惊厥潜伏期、强直率、死亡率及发作级别。结果 W_(112)能明显延长4种化学物质所致惊厥小鼠的惊厥潜伏期,显著降低惊厥鼠的强直率、死亡率及发作级别,且具有一定的量效关系。结论 W_(112)具有明显的抗癫痫作用,其作用机制主要是通过激活γ-氨基丁酸(GABA)神经递质系统,产生类GABA活性,从而起到抗癫痫作用。     

灵芝多糖肽对Alzheimer样大鼠海马超微结构和抗氧化能力的影响

目的 观察灵芝多糖肽(GLPP)对Alzheimer样大鼠海马超微结构、海马组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量以及空间学习记忆能力的影响.方法 雄性Wistar大鼠60只,随机分为对照组、模型组、NS组、GLPP组,每组15只.除对照组(正常昼夜节律)外,其余各组每天连续光照(光照度400 Lux)24 h,共30 d.其间GLPP组每天1次灌胃 GLPP(250 mg/kg);NS组灌胃相同体积的生理盐水.光照30 d后Morris水迷宫法测试各组大鼠空间学习记忆能力,黄嘌呤氧化酶法测定SOD活性,硫代巴比妥酸比色法测定MDA含量,透射电镜观察海马线粒体和突触结构的改变.结果 寻台潜伏期模型组大鼠较对照组明显延长(P＜0.05),GLPP组较模型组明显缩短(P＜0.05);NS组与模型组比较无显著差异.模型组较对照组海马SOD活性降低、MDA含量升高(P＜0.05);GLPP组较模型组SOD活性升高、MDA含量降低(P＜0.05);NS组SOD活性降低、MDA含量升高,与模型组比较无显著差异.透射电镜结果 显示:对照组、GLPP组大鼠海马线粒体神经轴突和神经突触基本正常;模型组和NS组大鼠海马线粒体膜结构破坏,线粒体肿胀,线粒体嵴模糊、消失,结构紊乱,神经髓鞘内神经细丝稀少,神经突触缺失、减少,突触密度降低,突触间隙不清,突触小泡减少.结论 GLPP可防止持续光照对大鼠海马超微结构的破坏和减轻Alzheimer样大鼠的空间记忆障碍.     

依托咪酯在大鼠最大电休克和戊四氮模型中的抗惊厥作用

目的研究依托咪酯在最大电休克(maximal electroshock seizure,MES)和戊四氮(metrazol seizure test,MST)惊厥实验中的抗惊厥作用。方法复制160只Wistar大鼠MES和MST模型,MES实验大鼠80只随机分为4组,分别为依托咪酯10 mg/kg组(E10组)、5 mg/kg组(E5组)、2.5 mg/kg组(E2.5组)和对照1组,每组20只。MST实验大鼠80只随机分为4组,分别为依托咪酯10 mg/kg组(E10组)、5 mg/kg组(E5组)、2.5 mg/kg组(E2.5组)和对照2组,每组20只。观察MES中大鼠的惊厥发生率、死亡率和强直持续期,MST中惊厥潜伏期、惊厥数和死亡数,并记录每只大鼠的发作强度。发作24 h后,灌注固定后取脑,常规HE染色及Nissl染色。结果在MES中,与对照1组比较,E2.5组可缩短强直持续期(P<0.05),对惊厥发生率无明显影响,E5组可同时缩短强直持续期(P<0.01)降低惊厥发生率,E10组可完全拮抗大鼠电惊厥的发生。在MST中,与对照2组比较,依托咪酯各组仍具明显抗惊厥作用,其抗惊厥作用具有剂量依赖性,用量越大,大鼠惊厥发生强度越小。结论依托咪酯在动物模型观察中,具有对抗癫癎发作的作用,有希望成为临床治疗癫癎发作的药物。     

葡萄籽原花青素提取物预灌胃对造影剂诱导糖尿病大鼠急性肾损伤的预防作用观察

目的 观察葡萄籽原花青素提取物预灌胃对造影剂诱导糖尿病大鼠急性肾损伤的预防作用,并探讨可能作用机制。方法 50只SD肥胖大鼠,腹腔注射1%链脲佐菌素（40 mg/kg）,41只成功建成糖尿病大鼠模型,随机分为DM组8只、CM组9只、葡萄籽原花青素提取物低剂量组8只、中剂量组8只、高剂量组8只,另取10只肥胖大鼠为空白对照组（NC组）,1 mL/kg腹腔注射柠檬酸缓冲液;低、中、高剂量组大鼠每日分别用50、250、500 mg/kg的葡萄籽原花青素提取物灌胃1次,连续3天,第3天灌胃24 h时尾静脉注射碘海醇（1.8 g I/kg）;NC组、DM组、CM组大鼠每日用10 mL/kg生理盐水灌胃1次,第3天灌胃24 h时,NC组、DM组尾静脉注射5 ml/kg生理盐水;CM组尾静脉注射碘海醇（1.8 g I/kg）。末次给药48 h时各组大鼠断尾采血,检测血清肌酐（SCr）和尿素氮（BUN）,采血后处死各组大鼠,取肾组织检测肾组织氧化应激指标超氧化物歧化酶（SOD）、丙二醛（MDA）,采用原位缺口末端标记法测算各组大鼠肾小管上皮细胞凋亡指数,采用Western Blotting法检测各组大...     

白金定痫片抗癫痫及神经保护的实验研究

目的观察白金定痫片对致痫大鼠抗癫痫及神经保护的作用。方法将47只SD雄性大鼠随机分为正常组、模型组、对照组、实验组。对照组、模型组予生理盐水,对照组予丙戊酸钠片,实验组予白金定痫片。每日1次灌胃给药,连续3d。于第3天灌胃给药后1h,正常组予腹腔注射生理盐水,其余组腹腔注射1%戊四唑60mg/kg,造癫痫模型。观察各组大鼠痫样发作行为,并测定大鼠海马部位的神经元特异性烯醇酶(NSE)的水平。结果与模型组比较,实验组大鼠完全停止发作时间缩短,重度发作发生率和死亡率都有所下降;其中完全停止发作时间上比较差异有统计学意义(P0.01);实验组NSE水平与模型组比较有差异有统计学意义(P0.01)。结论白金定痫片有一定的抗癫痫作用,对大鼠的海马部位神经元具有保护作用。     

5-脂氧酶表达与慢性铝过负荷致大鼠脑损伤的关系

目的 初步研究5-脂氧酶(LO)表达与慢性铝过负荷致大鼠脑损伤的关系.方法 灌胃给予大鼠葡萄糖酸铝(Al3+200 mg/kg),1次/d,5 d/w,持续20 w,建立慢性铝过负荷致大鼠脑损伤、神经元退变动物模型;5-LO抑制剂咖啡酸(30 mg/kg、10 mg/kg)分别在每次大鼠铝给予1 h后灌胃.以大鼠空间学习记忆能力改变、海马病理形态学变化以及脑组织5-LO蛋白和5-LO mRNA表达变化为观察指标.结果 慢性铝过负荷明显导致大鼠空间学习记忆能力下降、海马神经元损伤、脑组织5-LO蛋白和5-LO mRNA表达明显增加.给予咖啡酸能明显改善慢性铝过负荷大鼠的学习记忆能力障碍,明显减轻铝过负荷大鼠海马神经细胞的损伤,明显阻遏铝慢性过负荷诱导的5-LO蛋白和5-LO mRNA表达增加.结论 5-LO的过表达与慢性铝过负荷大鼠脑损伤、神经元退变之间存在着紧密的联系.     

Changes in brain amino acids and nitric oxide after melatonin administration in rats with pentylenetetrazole-induced seizures

We examined the effect of melatonin on brain levels of amino acids and nitric oxide (NO) after pentylenetetrazole (PTZ)-induced seizures in rats. Animals were treated with melatonin (10-160 mg/kg, i.p.) 30 min before PTZ administration (100 mg/kg, s.c.), and were killed 3 hr later. At the dose of 80 mg/kg, melatonin significantly increased the latency (5.7-12.7 min) and decreased the duration (31.2-18.4 s) of the first seizure, reducing PTZ induced mortality from 87.5 to 25%. After kill, brains were removed and neurotransmitters and nitrite levels measured in prefrontal cortex (PF), parieto-temporal cortex (PF), striatum (ST), hippocampus (HP) and brain stem (BS) by high performance liquid chromatography. PTZ treatment increased glutamine levels in all brain areas studied, without changes in glutamate, gamma-amino butyric acid (GABA) and glycine. Aspartate and taurine increased in PF and PT and in HS and PT, respectively. Melatonin administration displayed a dose-dependent effect. At doses of 10-40 mg/kg, melatonin counteracted the PTZ-induced glutamine increase and reduced both glutamate and aspartate levels in the studied areas, with minor changes in GABA and glycine content. At doses of 80 and 160 mg/kg, the levels of glutamine, and glutamate, and to a lesser extent aspartate increased, whereas serine levels did not change. These two doses of melatonin also increased taurine, GABA and glycine in most brain areas studied. Treatment with melatonin (40-160 mg/kg) significantly decreased nitrite content in PT cortex, ST and BS areas of epileptic rats, without changes in the other brain regions. The results suggest that the anticonvulsant property of melatonin involves a modulation of both brain amino acids and NO production.     

草药洋金花的抗惊厥作用研究

目的：观察洋金花原药对电刺激大鼠皮层惊厥阈值的影响，以明确其作为抗癫痫中药是否有进一步开发应用价值。方法：采用直接电刺激大鼠皮层惊厥阈值测定模型，将实验动物随机分为模型对照组、洋金花组、卡马西平组，分别测定给药前及给药后1h、5h的惊厥阈值。结果：洋金花组在给药后癫痫大鼠惊厥阈值明显增高，与对照组比较有统计学意义(P＜0．05)，随用药时间延长，其惊厥阈值与用药前比较亦渐升高(P＜0．05)，但其抗惊厥作用较卡马西平弱。结论：洋金花可能通过其所含生物碱——东莨菪碱的M—胆碱能受体阻断作用来发挥抗惊厥作用，其抗惊厥作用弱于卡马西平，但峰值持续时间长，这为中西医结合治疗癫痫，提供了一个新的方法。     

Further studies of the killing of M. leprae by aminoglycosides: reduced dosage and frequency of administration

The bactericidal activity of the aminoglycoside antibiotics streptomycin and kanamycin for Mycobacterium leprae in mice was assessed, both alone and in combination with rifampin, utilizing various dosage schedules. As in previous studies, 100 mg/kg five times weekly of streptomycin and kanamycin resulted, respectively, in 96% +/- 2% and 89% +/- 6% bactericide. Reducing the dosage of streptomycin to 50 mg/kg, 25 mg/kg, and even 12.5 mg/kg resulted in less but significant bactericidal activity. Such a reduction of kanamycin dosage resulted in no significant bactericidal activity. Reducing the frequency of administration of streptomycin (100 mg/kg) to twice weekly and once weekly resulted in a decreased but still significant killing of M. leprae; for kanamycin such a reduction in frequency of administration resulted in loss of bactericidal activity. Streptomycin when combined with rifampin was found more bactericidal than either drug alone, even when each was administered only once monthly.     

The N-methyl-D-aspartate receptor antagonist MK-801 delays the onset of puberty and may acutely block the first spontaneous LH surge and ovulation in the rat.

The physiological role of activated hypothalamic N-methyl-D-aspartate (NMDA) receptors during the final phase of female sexual maturation was explored in the rat. The effects of administration of the specific non-competitive receptor antagonist MK-801 on the occurrence of first ovulation and on LH secretion were studied. Injections of MK-801 (0.1-0.2 mg/kg body wt, s.c.) were given once or twice daily, starting at 28 or 35 days of age and continuing up to the day of first ovulation, resulted in a significant delay of this ovulation. Rats that were treated daily with 0.2 mg MK-801/kg, starting on days 30 or 34 and continuing up to day 38, but not including the day of first pro-oestrus, also showed retarded first ovulation. No decrease in serum LH concentration, compared with control rats, could be detected in these rats. Acute treatment with MK-801 (one or two injections of 0.2, or one injection of 0.5 mg/kg) given at 11.30 h (and 16.00 h) on the day of first pro-oestrus produced partial (1 x 0.2 mg/kg) or complete (2 x 0.2 and 1 x 0.5 mg/kg) blockade of first ovulation; blocked rats ovulated 1 day later. Serum LH concentrations at 16.00 h on the day of pro-oestrus were significantly decreased in all MK-801-treated groups compared with saline-injected control rats. At 19.00 and 22.00 h LH concentrations remained low in all non-ovulating MK-801-treated rats, but increased in the MK-801-treated rats and ovulated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethanol enhances GABAergic transmission onto dopamine neurons in the ventral tegmental area of the rat

Background:  Activation of the dopaminergic (DA) neurons of the ventral tegmental area (VTA) by ethanol has been implicated in its rewarding and reinforcing effects. At most central synapses, ethanol generally increases inhibitory synaptic transmission; however, no studies have explored the effect of acute ethanol on GABAergic transmission in the VTA.
Methods:  Whole-cell patch clamp recordings of inhibitory postsynaptic currents (IPSCs) from VTA-DA neurons in midbrain slices from young rats.
Results  Acute exposure of VTA-DA neurons to ethanol (25 to 50 mM) robustly enhanced GABAergic spontaneous and miniature IPSC frequency while inducing a slight enhancement of spontaneous IPSC (sIPSC) amplitude. Ethanol (50 mM) enhanced paired-pulse depression of evoked IPSCs, further suggesting enhanced GABA release onto VTA-DA neurons. The frequency of sIPSCs was suppressed by the GABA_B agonist, baclofen (1.25 μM) and enhanced by the antagonist, SCH50911 (20 μM); however, neither appeared to modulate or occlude the effects of ethanol on sIPSC frequency.
Conclusions:  The present results indicate that ethanol increases postsynaptic GABA_A receptor sensitivity, enhances action potential-independent GABA release onto VTA-DA neurons, and that this latter effect is independent of GABA_B auto-receptor inhibition of GABA release.     

Serotonergic stimulation of prolactin release in the young turkey (Meleagris gallopavo)

Serum prolactin (PRL) levels were determined by homologous radioimmunoassay in 6- to 10-week-old domestic white turkeys treated by intraperitoneal injection of agents that alter serotonergic activity. Quipazine (0.1–10.0 mg/kg), a serotonin (5-hydroxytryptamine; 5-HT) agonist, induced a dose-dependent rise in serum PRL level 1 hr after injection. The 5-HT precursor, 5-hydroxytryptophan (5-HTP), at doses of 80 and 150 mg/kg produced over a twofold elevation in PRL level 1 hr after administration, though the 50 mg/kg dose failed to produce any change. Administration of fluoxetine (10 mg/kg), a 5-HT reuptake blocker, induced an elevation in PRL level persisting 3 hr. When fluoxetine injection preceded administration of a weakly stimulatory dose of 5-HTP, a prolonged elevation in PRL level was observed. Methysergide (MES), a 5-HT antagonist, administered in a 10 mg/kg dose produced no change in PRL level, while the 25 mg/kg dose initially produced a spike in PRL level which subsequently dropped slightly below the control level. Prior injection of 20 mg/kg MES completely blocked the serum PRL rises induced by quipazine and 5-HTP. These results suggest that serotonergic mechanisms are involved in the regulation of pituitary PRL release beyond basal levels in young domestic turkeys.     

Oseltamivir prophylactic regimens prevent H5N1 influenza morbidity and mortality in a ferret model

BACKGROUND: Current oseltamivir prophylactic regimens may not be as effective against highly pathogenic H5N1 influenza viruses as they are against less pathogenic strains. An optimal regimen is urgently needed. METHODS: Ferrets were given the neuraminidase inhibitor oseltamivir orally for 10 days (5 or 10 mg/kg once daily or 2.5 or 5 mg/kg twice daily). Prophylaxis was initiated 1 day before infection, and oseltamivir was given 4 h before the ferrets were inoculated with a lethal dose of A/Vietnam/1203/04 (H5N1) influenza virus. RESULTS: At a dose of 5 mg/kg once daily, oseltamivir prevented death but not clinical signs of infection in ferrets; severe pathology was observed in the lungs, brain, and liver. At 10 mg/kg once daily, oseltamivir reduced clinical symptoms and systemic virus replication, but pathology was observed in the internal organs. The best results were obtained at a dose of 2.5 or 5 mg/kg given twice daily. Both regimens resulted in 100% survival and the absence of clinical symptoms, systemic virus spread, and organ pathology. Serum antibody titers were comparable across regimens and were sufficient to protect against rechallenge. CONCLUSIONS: An increased dose of oseltamivir or twice-daily administration effectively protects ferrets against morbidity and mortality caused by H5N1 infection and does not interfere with the development of protective antibodies against subsequent H5N1 infection.     

Photodynamic Therapy Using a New Photosensitizer Gallium Porphyrin Complex in the Treatment of Experimental Pancreatic Cancer

Abstract: To determine the therapeutic effect of photodynamic therapy (PDT) using a new photosensitizer 2.4-bis (1-decyloxyethyl)-Ca-deuteroporphyI diaspartic acid (Ga -DP), 20 female Syrian golden hamsters with experimentally induced pancreatic cancer were irradiated with a pulsed Nd : YAG laser with a Q switch after administration of Ga -DP. To induce pancreatic cancer, N-nitroso-bis-(2-oxypropyI) amine (BOP) at 10 mg/kg body weight was injected subcutaneously once a week for eight weeks. Ten of the twenty animals served as a control group. The other ten received laser treatment beginning 20 weeks after BOP administration. Twenty-four hours after intravenous injection of 3 mg/kg Ga-DP, pulsed Nd : YAG laser irradiation was performed using a Q switch with 1 W of power output for 3–5 minutes at a frequency of 300 Hz. Elimination or necrosis of the entire tumor resulted with tumors 6–10 mm in diameter in 6 animals. In 3 animals which had tumors more than 12 mm in diameter, cancer cells remained at the margins of the treated area. These results were felt to not only reflect the thermal effect of laser therapy, but also the effect of PDT combined with Ga-DP. They suggest that Ga-DP could become a clinically valuable photosensitizer in combination with PDT. (Dig Endosc 1994; 6 : 28–33)     

Effects of idebenone on metabolism of monoamines and cyclic AMP formation in rats

Idebenone, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone, at a dose of 100 mg/kg (i.p.) markedly increased the level of 5-hydroxyindole-3-acetic acid (5-HIAA) in several brain regions without affecting monoamine contents in normal rats. In rats with cerebral ischemia, idebenone (10 mg/kg, i.p.) normalized the decreased levels of 5-HIAA in the cerebral cortex, hippocampus, diencephalon and brain stem. A 5-hydroxytryptamine (serotonin, 5-HT) biosynthesis inhibitor, DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) decreased the levels of 5-HT to one-third of the control level 24 h after administration. Idebenone (10, 30, or 100 mg/kg, i.p.), administered 24 h after the treatment with PCPA, accelerated the PCPA-induced 5-HT decreased in the hippocampus, diencephalon and brain stem in a dose-dependent manner. Idebenone (100 mg/kg, i.p.) stimulated the release of 5-HT in the dorsal hippocampus as determined by in vivo differential pulse voltammetry. Idebenone, like p-chloroamphetamine (PCA), stimulated 5-HT release from slices of hippocampus and diencephalon, and the formation of cyclic AMP in a concentration-dependent manner in rat diencephalon slice. This stimulation was almost completely blocked by methysergide, a 5-HT receptor blocker. Idebenone slightly and PCA markedly inhibited 5-HT uptake into hippocampus slices. The mechanism of the 5-HT releasing actions of idebenone in the hippocampal slices may be mediated through endogenous calcium. These results suggest that idebenone has an enhancing effect on the turnover of 5-HT in the hippocampus, diencephalon, and brain stem of rats.