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首页> 外文期刊>The Internet Journal of Pharmacology >Tryptophan Adjunctive Therapy To Conventional Haloperidol Treatment In Schizophrenia: Effects On Serotonergic Mechanisms In Rat Brain
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Tryptophan Adjunctive Therapy To Conventional Haloperidol Treatment In Schizophrenia: Effects On Serotonergic Mechanisms In Rat Brain

机译：色氨酸辅助治疗精神分裂症中常规氟哌啶醇的治疗：对大鼠脑血清素能机制的影响。

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We studied the effects of dietary amino acid L-tryptophan (TRP) as an adjunct to haloperidol administration on the modulation of extrapyramidal symptoms (EPS) and rat brain serotonin (5-hydroxytryptamine; 5-HT) functions in relation to schizophrenia. TRP added in the drinking water and haloperidol at doses of 5.0 mg/kg or saline were injected for two weeks twice daily with one week of withdrawal to 36 locally bred male albino Wistar rats. Motor/ Exploratory activities were scored in activity boxes and open field apparatuses. Catalepsy was monitored on an inclined surface. Results revealed significant increases (p<0.01) in locomotor activity and marked reduction in catalepsy in rats orally supplemented with TRP for 3 weeks plus haloperidol administration. Significant (p<0.01) increases were observed in the rat brain TRP and 5-HT metabolism. The findings suggest that amino acids, in particular, TRP can possibly attenuate EPS functions induced by haloperidol and enhanced brain 5-HT metabolism. Introduction Modern medical science has made imposing progress in understanding the role of dietary amino acid supplementations in the maintenance of modern health and in the prevention of schizophrenia. Many of the neurotransmitter substances are present in foods, and therefore, can directly influence brain chemistry. Dietary factors 1 affecting the peripheral amino acid balance like carbohydrate and protein content influence the availability of the amino acid L-tryptophan (L-TRP) 1,2 for the central nervous system (CNS) and thus synthesis of 5-hydroxytryptamine (5-HT; serotonin). 2 5-HT is a chemical that produces from its precursor L-TRP in the CNS. The rate at which serotonergic neurons synthesize their 5-HT depends upon the availability of its precursor TRP. TRP is transported from the blood to the brain via an active carrier mechanism specific for this and other large neutral amino acids (LNAAs) like valine (VAL). 2 As a consequence, not the plasma concentration of TRP but the ratio of TRP to the sum of other five LNAAs (valine, leucine, isoleucine, tyrosine and phenylalanine) (TRP/ 5LNAAs ratio) reflects the best concentration of TRP in the CNS. 3,4 The administration of TRP or the consumption of carbohydrate rich diet/ meal all elevate brain TRP levels and, soon thereafter, the levels of serotonin and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA). 2 TRP occurs in low concentration (<1%) in most protein sources. In order to gain access to the brain, it must compete with other LNAAs via a common transport mechanism. Low protein diets sway the ratio of TRP to LNAA in favor of TRP, so that more TRP is transported into the brain (Fig1). Dietary supplementation of TRP can likewise increase the ratio of TRP to other LNAAs, and afford TRP an advantage when vying for entry into the brain. 3 It is, therefore, suggested that serotonin-containing neurons are under specific dietary control. L-VAL, a branched-chain amino acid (BCCA) competes with the TRP for transport into the brain and has previously been shown the decreased brain 5-HT synthesis. 5 However, it is reported that TRP load increases 5-HT synthesis in the brain and therefore may stimulate 5-HT release and functions. 4,6 In our study, effects of these amino acids manipulations are monitored on haloperidol-induced catalepsy and 5-HT metabolism in the medial prefrontal cortical (mPFC) region of rat brain. These findings will help to understand the role of serotonin in the precipitation of neuroleptic-induced catalepsy. The ability of antipsychotic drugs to modulate serotonergic as well as dopaminergic function has been suggested to be important for their efficacy and side-effect profile. 7 Motor-related side-effects are commonly encountered in the treatment of schizophreniform psychoses with so-called “classical” antipsychotic drugs such as haloperidol that are known to block central dopamine (DA) receptors 8,9 with their DA-D2 antagonistic potential. However, it is also know
机译：我们研究了饮食氨基酸L-色氨酸（TRP）作为氟哌啶醇的辅助治疗对锥体束外症状（EPS）和大鼠脑5-羟色胺（5-羟色胺; 5-HT）功能的调节与精神分裂症的关系。将以5.0 mg / kg或盐水的剂量添加到饮用水和氟哌啶醇中的TRP每天注射两次，每次两次，每周两次，停药一周则注射到36只本地繁殖的雄性白化Wistar大鼠中。在活动箱和野外仪器中对汽车/探索活动进行评分。在倾斜表面上监测僵直症。结果显示，口服补充了TRP的大鼠服用氟哌啶醇3周后，运动活性显着增加（p <0.01），并且僵直症明显减少。在大鼠脑TRP和5-HT代谢中观察到显着（p <0.01）增加。这些发现表明氨基酸，特别是TRP可能会减弱氟哌啶醇诱导的EPS功能并增强脑5-HT代谢。引言现代医学在理解膳食氨基酸补充剂在维持现代健康和预防精神分裂症中的作用方面取得了令人瞩目的进步。食物中存在许多神经递质，因此可以直接影响大脑的化学反应。饮食因素1影响周围氨基酸的平衡，例如碳水化合物和蛋白质含量，影响中枢神经系统（CNS）氨基酸L-色氨酸（L-TRP）1,2的利用率，从而影响5-羟色胺（5- HT; 5-羟色胺）。 2 5-HT是在CNS中由其前体L-TRP产生的化学物质。血清素能神经元合成其5-HT的速率取决于其前体TRP的可用性。 TRP通过这种和其他大型中性氨基酸（LNAA）（如缬氨酸（VAL））特有的活性载体机制从血液中运输到大脑。 2因此，不是TRP的血浆浓度而是TRP与其他五个LNAA（缬氨酸，亮氨酸，异亮氨酸，酪氨酸和苯丙氨酸）之和的比率（TRP / 5LNAAs比率）反映了CNS中TRP的最佳浓度。 3,4施用TRP或食用富含碳水化合物的饮食/膳食都会提高脑TRP水平，此后不久，血清素及其主要代谢物5-羟吲哚乙酸（5-HIAA）的水平就会升高。 2大多数蛋白质来源中的TRP浓度较低（<1％）。为了获得进入大脑的机会，它必须通过共同的运输机制与其他LNAA竞争。低蛋白饮食会影响TRP与LNAA的比例，从而有利于TRP，从而将更多的TRP转运到大脑中（图1）。膳食补充TRP可以同样增加TRP与其他LNAA的比例，并在争夺进入大脑的竞争时为TRP提供了优势。 3因此，建议含5-羟色胺的神经元受特定饮食控制。 L-VAL（一种支链氨基酸（BCCA））与TRP竞争转运到大脑中，并且先前已证明大脑5-HT合成减少。 5然而，据报道，TRP负荷会增加大脑中5-HT的合成，因此可能刺激5-HT的释放和功能。 4,6在我们的研究中，监测了这些氨基酸操作对氟哌啶醇诱导的大鼠大脑内侧前额叶皮层（mPFC）区域中的僵硬度和5-HT代谢的影响。这些发现将有助于了解5-羟色胺在精神安定药引起的僵直症发作中的作用。已建议抗精神病药调节血清素能和多巴胺能功能的能力对其功效和副作用特征很重要。 7与运动相关的副作用通常是在用所谓的“经典”抗精神病药（如氟哌啶醇）治疗精神分裂症性精神病时遇到的，这些药物已知会阻断DA-D2拮抗作用，从而阻断中枢多巴胺（DA）受体8,9。但是，也知道

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