Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice

Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was induced in mice with haloperidol (1.0 mg/kg, intraperitoneally). The first group received the vehicle (10 ml/kg, orally), the second group received trihexyphenidyl (10 mg/kg, orally) and the remaining two groups received Tribulus terrestris (100, 200 mg/kg, orally). The animals were assessed after single and repeated dose administration for ten days, 30 min prior to haloperidol, using standard bar test. The result of the present study demonstrates Tribulus terrestris has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drug used for the same purpose. Our study indicates Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal side effects.     

苯海索对大鼠急性前脑缺血再灌注损伤的保护

目的：研究苯海索（ｔｒｉｈｅｘｙｐｈｅｎｉｄｙｌ，ＴＨＰ）对大鼠急性前脑缺血再灌注损伤的保护作用。方法：用阻断四血管法造成急性前脑缺血再灌注损伤。ＴＨＰ１．５ｍｇ·ｋｇ－１或３ｍｇ·ｋｇ－１在缺血前５ｍｉｎ，再灌前和再灌注３０ｍｉｎ分３次静脉注射。结果：ＴＨＰ可剂量依赖性阻止脑组织和红细胞中超氧化物歧化酶活力下降及脑组织中乳酸脱氢酶（ＬＤＨ）活力下降，阻止外周血中ＬＤＨ活力增加和过氧化脂质含量增加，并促进脑电活动恢复和抑制脑水肿形成。结论：ＴＨＰ对大鼠急性前脑缺血再灌注损伤具有保护作用，其机制与抗脂质过氧化有关。     

左旋盐酸去甲基苯环壬酯对大鼠和小鼠震颤与行为的影响

目的评价抗胆碱药左旋盐酸去甲基苯环壬酯(R-DM8021)的帕金森病(PD)治疗作用。方法 ①使用脑单侧立体定向注射6-羟基多巴胺(6-OHDA)损毁大鼠中脑黑质-多巴胺神经元的方法建立PD动物模型。观察大鼠单次ig给予R-DM80210.2,0.5,1.0和2.0mg.kg-1旋转行为;观察大鼠连续ig给予R-DM80210.2,0.5和2.0mg.kg-121d对大鼠旋转行为;观察大鼠连续ig给予R-DM80210.2,0.5和2.0mg.kg-17d后自发活动情况。②昆明小鼠ig给予R-DM80210.25～40mg.kg-1,30min后ip给予氢溴酸槟榔碱35mg.kg-1,观察肌肉震颤持续时间。③C57BL/6小鼠ip给予MPTP30mg.kg-17d建立MPTP帕金森病模型,ig给予R-DM80215,10和20mg.kg-1后观察小鼠自发活动情况。结果①与6-OHDA损毁模型对照组相比,单次ig给予R-DM80210.2,0.5,1.0和2.0mg.kg-1分别使APO诱导的旋转次数增加(17.3±4.5)%、(29.8±9.3)%、(30.2±13.9)%和(31.7±5.5)%;苯海索3.0,5.0和10.0mg.kg-1组分别增加(18.8±4.8)%、(22.2±17.3)%和(36.9±10.0)%。连续给药21d,大鼠APO诱导的旋转次数显著增加(P<0.01),并维持在稳定的水平。与等剂量的苯海索相比,R-DM8021对APO诱导旋转的作用更强。建模成功后,大鼠10min内自发活动路程较正常组显著降低(P<0.01),连续给予R-DM8021和苯海索7d可明显提高大鼠自发活动路程,R-DM8021对大鼠自发活动的改善效果显著优于等剂量的苯海索(P<0.01)。②ip给予槟榔碱35mg.kg-1,小鼠出现明显肌肉震颤,持续时间为(8.9±1.0)min,R-DM8021和苯海索均可剂量依赖性地降低小鼠肌肉震颤持续时间,两药对槟榔碱致小鼠肌肉震颤持续时间抑制作用的ED50分别为(6.87±1.33)mg.kg-1和(41.14±9.31)mg.kg-1,两者相比具有显著性差异(P<0.01)。③ip连续给予MPTP7d,小鼠3min内自发活动路程较正常组显著降低,连续ig给予R-DM8021和苯海索3d可明显提高小鼠自发活动路程,R-DM8021对小鼠自发活动的改善效果显著优于等剂量的苯海索(P<0.01)。结论 R-DM8021对3种模型PD均有治疗作用且效果均优于苯海索。     

Interactions between neurons in the frontal cortex and hippocampus in cats trained to select reinforcements of different value in conditions of cholinergic deficiency

An operant food-related conditioned reflex was developed in six cats by the “active choice” protocol: short-latency pedal presses were followed by presentation of low-quality reinforcement (bread-meat mix), while long-latency pedal presses were followed by presentation of high-quality reinforcement (meat). Animals differed in terms of their food-procuring strategies, displaying “self-control,” “ambivalence,” or “impulsivity.” Multineuron activity was recorded from the frontal cortex and hippocampus (field CA3). Cross-correlation analysis of interneuronal interactions within (local networks) and between (distributed networks) study structures showed that the numbers of interneuronal interactions in both local and distributed networks were maximal in animals with “self-control.” On the background of systemic administration of the muscarinic cholinoreceptor blockers scopolamine and trihexyphenidyl, the numbers of interneuronal interactions decreased, while “common source” influences increased. This correlated with impairment of the reproduction of the selected strategy, primarily affecting the animals’ self-controlled behavior. These results show that the “self-control” strategy is determined by the organization of local and distributed networks in the frontal cortex and hippocampus. __________ Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 56, No. 5, pp. 653–663, September–October, 2006.     

Primary lingual dystonia induced by speaking.

We describe a 46-year-old woman who presented with lingual dystonia induced only by speaking, which responded well to anticholinergic treatment.     

Trihexyphenidyl Potentiation ofl-DOPA: Reduced Effectiveness Three Years Later in MPTP-Induced Chronic Hemiparkinsonian Monkeys

The effects of a combination of trihexyphenidyl andl-DOPA methyl ester given i.m. were studied 3–5 years after MPTP induced hemiparkinsonism in five female adultMacaca nemistrinamonkeys. Three years later, these studies were repeated to determine if the drug combination was equally effective. Although the combination of trihexyphenidyl andl-DOPA produced potentiation in both studies, 3 years later it was quantitatively less. This was due primarily to the reduced effectiveness ofl-DOPA methyl ester in a dose of 12.5 mg/kg i.m. Even though the combination was less effective in subsequent years, the animals continued to show the same clinical signs of hemiparkinsonism. Reduced effectiveness of the drug combination does not appear to be due to a lessening of MPTP-induced hemiparkinsonism, but rather to the reduced effectiveness ofl-DOPA.     

Functional activity of the sensorimotor cortex and cerebellum relates to cervical dystonia symptoms

Cervical dystonia (CD) is the most common type of focal dystonia, causing abnormal movements of the neck and head. In this study, we used noninvasive imaging to investigate the motor system of patients with CD and uncover the neural correlates of dystonic symptoms. Furthermore, we examined whether a commonly prescribed anticholinergic medication in CD has an effect on the dystonia‐related brain abnormalities. Participants included 16 patients with CD and 16 healthy age‐matched controls. We collected functional MRI scans during a force task previously shown to extensively engage the motor system, and diffusion and T1‐weighted MRI scans from which we calculated free‐water and brain tissue densities. The dystonia group was also scanned ca. 2 h after a 2‐mg dose of trihexyphenidyl. Severity of dystonia was assessed pre‐ and post‐drug using the Burke–Fahn–Marsden Dystonia Rating Scale. Motor‐related activity in CD was altered relative to controls in the primary somatosensory cortex, cerebellum, dorsal premotor and posterior parietal cortices, and occipital cortex. Most importantly, a regression model showed that increased severity of symptoms was associated with decreased functional activity of the somatosensory cortex and increased activity of the cerebellum. Structural imaging measures did not differ between CD and controls. The single dose of trihexyphenidyl altered the fMRI signal in the somatosensory cortex but not in the cerebellum. Symptom severity was not significantly reduced post‐treatment. Findings show widespread changes in functional brain activity in CD and most importantly that dystonic symptoms relate to disrupted activity in the somatosensory cortex and cerebellum. Hum Brain Mapp 38:4563–4573, 2017. © 2017 Wiley Periodicals, Inc.     

苯海索对培养大鼠神经细胞缺氧/缺糖性损伤的保护作用

目的 观察苯海索对缺血／缺氧培养所致大鼠皮层神经细胞损伤的保护作用。方法 体外培养大鼠胚胎皮层神经细胞，以缺氧加缺糖培养建立神经细胞“缺血”性损伤模型，观察苯海索对培养神经细胞”性损伤的保护作用。结果 苯海索能显著减少细胞死亡，降低乳酸脱氢酶（LDH）漏出量、一氧化氮（NO）含量及丙二醛（MDA）生成，提高超氧化物歧化酶（SOD）活性。结论 苯海索对培养神经细胞“缺血”性损伤具有显著的保护作用，其机制可能与苯海索降低NO含量、抗过氧化作用有关。     

Motor and Sensory Dysfunction in Musician’s Dystonia

Musicians’ dystonia is a task-specific and painless loss of motor control in a previously well-executed task. It is increasingly recognized in the medical and musical community. Recent advances in neuroimaging, transcranial magnetic stimulation and novel techniques in electroencephalography have shed light on its underlying pathophysiology. To date, a deranged cortical plasticity leading to abnormal sensorimotor integration, combined with reduced inhibition across several levels of the motor pathway are likely mechanisms.This paper reviews the various phenomenology of musician’s dystonia across keyboard, string, brass, flute and drum players. Treatment is often challenging. Medical therapies like botulinum toxin injection and rehabilitation method with sensorimotor training offer symptomatic relief and return to baseline performance to some musicians.     

Simultaneous Spectrophotometric Estimation of Haloperidol and Trihexyphenidyl in Tablets

The combination of haloperidol and trihexyphenidyl is a dosage form to be used as antidyskinetic agent. Literature revealed that there is no single method for the simultaneous estimation of these drugs in tablet dosage form, which prompted us to develop a simple, rapid, accurate, economical and sensitive spectrophotometric method. The simultaneous estimation method is based on the principle of additivity of absorbance, for the determination of haloperidol and trihexyphenidyl in tablet formulation. The absorption maxima of the drugs were found to be at 245.0 nm and 206.0 nm respectively for haloperidol and trihexyphenidyl in methanol and 0.1N HCl (90:10). The obeyance of Beer Lambert’s law was observed in the concentration range of 2.5-12.5 µg/ml for haloperidol and 1.0-5.0 µg/ml for trihexyphenidyl. The accuracy and reproducibility of the proposed method was statistically validated by recovery studies.