Potential antidepressant effect of amantadine: a review of preclinical studies and clinical trials

Objective: Amantadine blocks N-methyl-D-aspartate (NMDA) receptors and has dopaminergic and noradrenergic action, a neurochemical profile that suggests its potential as an antidepressant drug. We conducted a systematic review of preclinical and clinical studies addressing the effects of amantadine in animal models of depression and in patients with depression. Methods: PubMed, Science Direct, and Web of Science were searched up to September 1, 2017 to identify clinical and preclinical studies. The following search terms were used: "amantadine AND depress*"; "amantadine AND mood"; "amantadine AND animal models AND antidepres*"; and "amantadine AND (forced swim, learned helplessness, reserpine, chronic mild stress, anhedonia, sucrose preference)." Results: Amantadine had antidepressant-like effects in animal models and appeared to potentiate the antidepressant effects of other antidepressants. These preclinical findings have received some support from the results of small open-label clinical trials, suggesting that amantadine can reduce depressive symptomatology and potentiate the antidepressant effects of monoaminergic drugs. In addition to its glutamatergic and dopaminergic effects, the potential antidepressant-like effects of amantadine have been linked to molecular and cellular actions, such as increased expression of neurotrophic factors (e.g., brain-derived neurotrophic factor), activation of σ1 receptors, decreased corticosterone levels, and decreased inflammatory response to stress. Conclusion: Amantadine is an interesting candidate as new antidepressant drug for the treatment of depression.

Mesilato de rasagilina em combinação com levodopa para o tratamento de pacientes com doença de Parkinson com complicações motoras / Rasagiline mesylate in combination with levodopa for the treatment of patients with Parkinson's disease with motor complications

CONTEXTO: a doença de Parkinson (DP) tem distribuição universal e atinge a todos os grupos étnicos e classes socioeconômicas, com uma discreta predominância no sexo masculino. É a segunda desordem neurodegenerativa mais frequente, estando atrás apenas da doença de Alzheimer (1). A prevalência em países industrializados é estimada ao redor de 0,3% para toda a população, chegando a cerca de 1 a 4% na população acima de 65 anos. A incidência varia entre 8 a 18 casos por 100.000 pessoas-ano. No Brasil, um estudo de base populacional identificou prevalência de 3,3% para a DP entre maiores de 60 anos (2). Embora a idade seja o principal fator de risco para a doença, com claro aumento da prevalência e da incidência com o envelhecimento da população, há casos em pacientes jovens, principalmente formas monogênicas, que ocorrem em cerca de 10% do total de casos (1). É um doença crônica e progressiva, caracterizada por sintomas motores e não-motores, que provoca incapacidade funcional e aumento da mortalidade. O tratamento da DP consiste no uso de medicamentos que proporcionam estímulo dopaminérgico, principalmente a levodopa, o que possibilita um controle quase ótimo dos sintomas motores nos primeiros anos de uso. Entretanto, em aproximadamente cinco anos, cerca de metade dos pacientes apresentarão complicações motoras induzidas pelo uso crônico desta medicação, o que determina piora da qualidade de vida. As principais complicações são a flutuação da resposta motora (perda do efeito terapêutico antes do esperado e/ou de forma súbita) e discinesia (movimentos involuntários hipercinéticos). De acordo com o PCDT de 2010 para DP(3), o manejo da flutuação motora induzida por levodopa é feito com a associação de agonistas dopaminérgicos (bromocriptina ou pramipexol) e/ou inibidores da COMT (entocapona e tolcapona). Dados do DATASUS mostram que no ano de 2015 cerca de 50 mil pessoas faziam uso dessas medicações no Brasil. TECNOLOGIA: Mesilato de rasagilina (AZILECT®). INDICAÇÃO: pacientes com doença de Parkinson em uso de levodopa com complicações motoras. PERGUNTA: O uso de mesilato de rasagilina como terapia adjuvante à levodopa é eficaz e segura no tratamento de pacientes com DP com complicações motoras quando comparado ao uso de agonistas dopaminérgicos e inibidores da COMT disponíveis no SUS? EVIDÊNCIAS CIENTÍFICAS: o principal estudo apresentado pelo demandante é uma revisão sistemática com meta-análise de 44 ensaios clínicos para avaliar os tratamentos disponíveis para doença de Parkinson em uso de levodopa com complicação motora. Três estudos avaliaram a tecnologia proposta pelo demandante, um com comparador ativo (entacapona) e os outros comparados contra placebo. Como resultado, o mesilato de rasagilina 1mg uma vez ao dia foi eficaz no controle das complicações motoras de pacientes com DP em uso de levodopa. As medidas de eficácia mais importantes foram redução do tempo de off e da dose de levodopa e melhora da escala UPDRS. Em comparações indiretas, os agonistas dopaminérgicos foram melhores do que os inibidores da COMT e os inibidores da MAOB (incluindo rasagilina). Esses dois últimos foram semelhantes entre si. Em relação à segurança, os inibidores da MAOB apresentaram menos efeitos adversos em comparação com as outras duas classes, especialmente no que se refere ao surgimento da discinesia induzida por levodopa. As principais limitações deste estudo foram o (1) potencial viés de publicação, que não foi adequadamente avaliado, (2) as comparações, em sua maioria, indiretas e (3) a heterogeneidade entre os estudos. AVALIAÇÃO ECONÔMICA: utilizou-se um modelo de custo-minimização, considerando a população definida na pergunta PICO e um horizonte temporal de um ano, pela perspectiva do SUS. Os comparadores foram as alternativas atualmente disponíveis no SUS e o desfecho foi o custo anual. O uso da rasagilina representou uma redução de custo entre 57% a 78% entre os anos de 2017 a 2021, a depender do comparador escolhido. Esse resultado manteve-se favorável à nova tecnologia após análise de sensibilidade. A principal limitação é que foi um modelo de custo-minimização quando a maioria das comparações entre as drogas foi indireta. O mais adequado seria um modelo pleno de custo-efetividade. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: A população elegível para o estudo de impacto orçamentário considerou estimativas baseadas em dados extraídos do DATASUS do número de pacientes com DP em uso de qualquer um dos medicamentos comparadores. Os custos anuais de cada tratamento foram obtidas na análise econômica. Como resultado, considerando um período de cinco anos (2017-2021), projetou-se uma economia de R$ 184,45 milhões de recursos do SUS.(AU)

Effect of Zuogui Pill () on monoamine neurotransmitters and sex hormones in climacteric rats with panic attack / 中国结合医学杂志

<p><b>OBJECTIVES</b>To explore the effects of Chinese medicine prescription Zuogui Pill (, ZGP) on monoamine neurotransmitters and sex hormones in climacteric rats with induced panic attacks.</p><p><b>METHODS</b>Forty-eight climacteric female rats were randomized into 6 groups with 8 rats in each group: the control group, the model group, the low-, medium- and high-dose ZGP groups and the alprazolam group. Rats in the low-, medium- and high-dose ZGP groups were administered 4.725, 9.45, or 18.9 g/kg ZGP by gastric perfusion, respectively. The alprazolam group was treated by gastric perfusion with 0.036 mg/kg alprazolam. The control and model groups were treated with distilled water. The animals were pretreated once daily for 8 consecutive weeks. The behaviors of rats in the open fifield test and the elevated T-maze (ETM) were observed after induced panic attack, and the levels of brain monoamine neurotransmitters and the plasma levels of sex hormones were measured.</p><p><b>RESULTS</b>Compared with the control group, the mean ETM escape time and the levels of 5-hydroxytryptamine (5-HT) and noradrenalin (NE) of the model group were signifificantly reduced (P<0.05), Compared with the model group, the mean ETM escape time and the 5-HT and NE levels of all the ZGP groups increased signifificantly (P<0.05 or P<0.01). However, no signifificant difference was observed in the levels of sex hormones between the groups.</p><p><b>CONCLUSION</b>Pretreatment with ZGP in climacteric rats may improve the behavior of panic attack, which may be related to increased 5-HT and NE in the brain.</p>

Effects of Kaixin San formulas on behavioristics and central monoamine neurotransmitters of chronic stress rats / 中国中药杂志

The efficacy of Chinese herbal formula in treating depression has been proved in many studies. In this study, six different Kaixin San formulas were compared to investigate their effects on central monoamine neurotransmitters of chronic stress rats and against depression based on their different components in plasma, in order to discuss the efficacy-comparability relationship and the possible efficacy mechanism. The classic isolation method and the chronic unpredictable mild stress (CUMS) depression model were combined to investigate the changes in contents in hippocampus and monoamine neurotransmitters (NE, DA, 5-HT) and the components of some formulas in plasma with HPLC and UPLC-Q-TOF-MSE methods. As a result, Dingzhi Xiaowan recorded in Essential Recipes for Emergent Use Worth A Thousand significantly increased the behavioral scores, NE and 5-HT contents in hippocampus and NE, DA and 5-HT contents in cortex, with the best anti-depressant effect. Dingzhi Xiaowan recorded in Complete Records of Ancient and Modern Medical Works showed a notable increase in sucrose preference and open field score in model rats, NE content in hippocampus and NE, DA and 5-HT contents in cortex, with a certain anti anti-depressant effect. Kaixin San recorded in Ishinpo showed remarkable rise in weight of model rats. NE content in hippocampus and DA content in cortex. Puxin Decoction recorded in A Supplement to Recipes Worth A Thousand Gold showed 5-HT content in hippocampus and DA content in cortex. Kaixin San recorded in Yimenfang only showed DA content in cortex. Kaixin Wan recorded in Essential Recipes for Emergent Use Worth A Thousand did not mention the antidepressant effect. According to the results, the formulas' different anti-depressant effects may be related to the different plasma components.

Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy

A ketogenic diet is an important therapy used in the control of drug-refractory seizures. Many studies have shown that children and adolescents following ketogenic diets exhibit an over 50% reduction in seizure frequency, which is considered to be clinically relevant. These benefits are based on a diet containing high fat (approximately 90% fat) for 24 months. This dietary model was proposed in the 1920s and has produced variable clinical responses. Previous studies have shown that the mechanisms underlying seizure control involve ketone bodies, which are produced by fatty acid oxidation. Although the pathways involved in the ketogenic diet are not entirely clear, the main effects of the production of ketone bodies appear to be neurotransmitter modulation and antioxidant effects on the brain. This review highlights the impacts of the ketogenic diet on the modulation of neurotransmitters, levels of biogenic monoamines and protective antioxidant mechanisms of neurons. In addition, future perspectives are proposed. .

Effect of monoamine neurotransmitter on megakaryocytopoiesis and platelet functions / 中国实验血液学杂志

The nervous system directly regulates immunity through neurotransmitter receptors expressed on immune cells to participate in host defense and body reparation. Expression of neurotransmitter receptors on blood cells provides important evidence for a direct functional link between the nervous and hematopoietic systems. Our previous studies showed that 5-hydroxytryptamine, as a monoamine neurotransmitter, plays an important role in regulating megakaryocytopoiesis. This review summarizes recent findings of the effect of monoamine neurotransmitter on megakaryocytopoiesis and platelet function, focusing on the receptor expression on hematopoietic stem cells, megakaryocytes/platelets and their functions in order to explore the intrinsic relation of nervous system and hematopoietic system. Based on the existing research results, we find that the monoamine neurotransmitter participates in regulation of megakaryocytopoiesis, and affects on aggregation and functions activation of platelets. Moreover, it has a close link with the specific regulatory factor of megakaryocytopoiesis-TPO. Thus those results also support the "brain-bone marrow-blood-axis" viewpoint of some researchers. At present, the study of the nervous system regulating hematopoiesis is still in its infancy, the exact mechanism remains to be further studied.

Effects of Kaixin Jieyu Decoction () on behavior, monoamine neurotransmitter levels, and serotonin receptor subtype expression in the brain of a rat depression model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the mechanisms underlying the anti-depressant effects of Kaixin Jieyu Decoction (, KJD) by investigating the effects of KJD on behavior, monoamine neurotransmitter levels, and serotonin (5-HT) receptor subtype expression in the brain in a rat model of depression.</p><p><b>METHODS</b>The rat depression model was established using chronic unpredictable mild stress (CUMS). Forty-eight Sprague Dawley rats were randomly divided into control, depression model (CUMS), CUMS+KJD (7.7 g/kg(-1)·d(-1) of crude drug), and CUMS+fluoxetine (2.4 mg/kg(-1)·d(-1)) groups (n=12 in each group), and the treatments lasted for 21 days. We regularly evaluated body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests. The content of the monoamine neurotransmitters 5-HT, norepinephrine (NE), and dopamine (DA) and the DA metabolite homovanillic acid in the cerebral cortex, and 5-HT1A and 5-HT2A receptor mRNA in the cerebral cortex and the hippocampus, were determined respectively by high-performance liquid chromatography-coularray electrochemical detector and real-time polymerase chain reaction.</p><p><b>RESULTS</b>Compared with the control group, CUMS rats showed a variety of depression-like behavioral changes, including a significant reduction in body weight, sucrose consumption, and horizontal and vertical activity scores in open-field tests (P<0.05 or P<0.01), and a significant decrease in 5-HT and NE levels and 5-HT2A receptor mRNA expression. In contrast, they showed a significant increase in 5-HT1A receptor mRNA expression in the cerebral cortex. In the hippocampus, 5-HT1A receptor mRNA expression was lower whereas 5-HT2A receptor mRNA expression was higher than in the control group (P<0.05 or P<0.01). Treatment with KJD or fluoxetine partially attenuated these changes (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>KJD could normalize the levels of 5-HT and NE and adjust the balance of 5-HT1A and 5-HT2A receptor expression in rat cerebrum, and this may be one of mechanisms of antidepressant effects of KJD.</p>

Analysis of correlation between occupational stress and serum monoamine neurotransmitters in nurses / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the impact of occupational stress on serum monoamine neurotransmitters in nurses.</p><p><b>METHODS</b>A total of 131 nurses were included as study subjects by stratified cluster sampling. The occupational health information collection system (based on the Internet of things) was used to measure occupational stress. Serum levels of monoamine neurotransmitters were also measured.</p><p><b>RESULTS</b>Epinephrine (E) was negatively correlated with superior support (P < 0.05) and colleague support (P < 0.05). Negative correlation was also found between dopamine (DA) and job prospect (P < 0.05). Level of 5-hydroxytryptamine was negatively correlated with promotion opportunities (P < 0.05). Norepinephrine (NE), E, and DA were all negatively correlated with work satisfaction (P < 0.05) and positively correlated with daily stress (P < 0.01). NE and E were negatively correlated with sufficient confidence (P < 0.05) and positively correlated with physical complaints (P < 0.01). There was a negative correlation between NE and psychological satisfaction (P < 0.05).</p><p><b>CONCLUSION</b>Occupational stress in nurses is correlated with serum monoamine neurotransmitters, and it may affect serum levels of monoamine neurotransmitters to a certain extent.</p>

Analgesic effect of sinomenine on SSNI model rats and monoamine neurotransmitters in striatal extracellular fluid / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the analgesic effect of sinomenine on the neuropathic pain rat model induced by SSNI, and discuss its impact on monoamine neurotransmitters in striatal extracellular fluid.</p><p><b>METHOD</b>Male SD rats were randomly divided into the sham operation group, the SSNI model group, the gabapentin group (100 mg x kg(-1)), the sinomenine high dose group (40 mg x kg(-1)) and the sinomenine low dose group (20 mg x kg(-1)). Mechanical hyperalgesia and cold pain sensitivity were evaluated by Von Frey hairs and cold spray. Striatum was sampled by microdialysis. High performance liquid chromatography-electrochemical detector (HPLC-ECD) were used to detect the content of such neurotransmitters as monoamine neurotransmitters noradrenaline (NE), dopamine (DA), 5-hydroxy tryptamine (5-HT) and their metabolites dihydroxyphenylacetic phenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA).</p><p><b>RESULT</b>SSNI model rats showed significant improvement in mechanical withdrawal threshold and cold pain sensitivity, significant decrease in intracerebral NE and notable increase in DA, 5-HT and their metabolites. Compared with the model group, the sinomenine high dose group showed significant increase in mechanical withdrawal threshold at 60, 90, 180 and 240 min after abdominal administration (P < 0.01), significant decrease in cold pain sensitivity score during 30-240 min (P < 0.05). Sinomenine can significantly up-regulated NE content in striatal extracellular fluid during 45-135 min (P < 0.05), remarkably reduce DA content and DOPAC at 45, 75 and 135 min (P < 0.05), 5-HT content during 45-135 min, DOPAC during 75-165 min (P < 0.05), and 5-HIAA during 45-135 min (P < 0.05).</p><p><b>CONCLUSION</b>Sinomenine has the intervention effect on neuropathic pain in SSNI model rats. Its mechanism may be related to disorder of monoamine neurotransmitters in striatal extracellular fluid.</p>

Effects of theanine on monoamine neurotransmitters and related genes in cerebral ischemia-reperfusion injury rats / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the effects of theanine on dopamine (DA), 5-hydroxy tryptamine (5-TH) and glutamate receptor 2 (GluR2) mRNA, phospholipase-γ1 (PLC-γ1) mRNA in cerebral ischemia-reperfusion injury rats and explore the mechanism of protective effects of theanine on the induced brain injury by ischemia-reperfusion in rats.</p><p><b>METHODS</b>According to random number table, a total of 56 sprague-dawley rats in SPF grade about six-week old and 100 - 120 grams weighting were divided into five groups according to the body weight levels: model group (n = 12), sham-operation group (n = 8), low theanine group (10 mg/kg), middle theanine group (30 mg/kg) and high theanine group (90 mg/kg). There were 12 rats in each of the theanine group. The rats in model group and sham-operation groups were given distilled water, and the rats in theanine groups were given corresponding theanine solution intragastrically for fifteen days. Then the cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion (MCAO). The score of neurological behavior was evaluated at the 3rd and 24th hours after reperfusion. Rats were sacrificed at 24 hours after reperfusion, the concentrations of DA, 5-HT and theanine in rats brain following ischemia-reperfusion were determined. At the same time, we determined the levels of reactive oxygen species (ROS) and activities of catalase (CAT) in mitochondria of brain. The expressions of GluR2 mRNA and PLC-γ1 mRNA in rat brain were examined by reverse transcription polymerase chain reaction (RT-PCR) technique.</p><p><b>RESULTS</b>The score of neurological behavior of rats in model group, theanine-low, middle, high dose groups at the 3rd hour was 6.000 ± 0.926, 4.100 ± 0.738, 3.444 ± 0.726 and 2.250 ± 0.886 respectively (F = 29.70, P < 0.01), and the score at the 24th hour in these groups was 6.625 ± 0.916, 5.000 ± 0.817, 3.667 ± 0.707 and 2.625 ± 0.916 respectively(F = 34.68, P < 0.01). The concentration of DA in model group, theanine-low, middle, high dose groups and sham-operation group was (10.26 ± 1.12), (12.48 ± 1.09), (14.55 ± 0.94), (15.97 ± 0.92) and (11.98 ± 0.63) µg/g respectively (F = 43.76, P < 0.01). The concentration of 5-HT in these groups was (1.091 ± 0.160), (0.818 ± 0.101), (0.571 ± 0.050), (0.453 ± 0.111) and (0.863 ± 0.063) µg/g respectively (F = 48.68, P < 0.01). The level of ROS was (3.072 ± 0.503), (1.331 ± 0.268), (1.295 ± 0.061), (0.804 ± 0.200) and (2.158 ± 0.218) U×min⁻¹×mg⁻¹ (F = 80.82, P < 0.01) respectively and the activities of CAT in these groups were (4.880 ± 1.121), (8.405 ± 1.356), (9.535 ± 2.511), (15.090 ± 4.054) and (21.260 ± 6.054) U/g respectively (F = 28.58, P < 0.01). The expressions of GluR2 mRNA were 0.842 ± 0.020, 1.063 ± 0.100, 1.170 ± 0.152, 1.254 ± 0.131 and 1.012 ± 0.056 respectively (F = 9.23, P < 0.01). The expressions of PLC-γ1 mRNA in these groups were 0.737 ± 0.090, 0.887 ± 0.045, 0.963 ± 0.025, 0.991 ± 0.049 and 0.867 ± 0.079 respectively(F = 10.24, P < 0.01).</p><p><b>CONCLUSION</b>Theanine has a protective effect on the induced brain injury by ischemia-reperfusion in rats, which might be associated with its interaction with monoamine neurotransmitters and up-regulating the expressions of GluR2 mRNA and PLC-γ1 mRNA.</p>

Detection of monoamine neurotransmitters and its metabolites by high performance liquid chromatograph after pre-column derivatization of dansyl chloride column / 中华预防医学杂志

<p><b>OBJECTIVE</b>To develop a high performance liquid chromatography (HPLC) for detection of monoamine neurotransmitters and its metabolites after pre-column derivatization with dansyl chloride.</p><p><b>METHODS</b>The C(18) chromatograph column (150 mm×4.6 mm×5 µm) was selected for detection, and derived by dansyl chloride (10 mg/ml) under the condition of 50°C water bath by pH11 buffer solution. 20 µl acetic acid acetone solution (1.0 mol/L) was then mixed in for termination of the reaction. Then the solution was cooling to room temperature, 0.1 mol/L acetic acid zinc-acetonitrile-tetrahydrofuran solution was adopted for mobile phrase, with the volume ratio at 62:35:3. The flow rate was 1.0 ml/min between 0-10 min, 2.0 ml/min between 10-35 min. The ultraviolet detection wavelength was 286 nm. The above method separately detected monoamine neurotransmitters and its metabolites and evaluated the limit of detection, accurate degree and accuracy degree.</p><p><b>RESULTS</b>The linear relations between each component was good in the range of 1 - 20 µg/ml (r = 0.999). The lowest detection limit of norepinephrine, dopamine, 5-hydroxytryptamine and the metabolites 3-methoxy-4-benzoglycols, homovanillic acid and 5-heteroauxin were separately 0.60, 0.80, 0.41, 0.21, 0.19 and 0.1 µg/ml; while the average recovery rates were between 78.5% - 95.9%, and the relative standard deviation (RSD) was 6.62%, 7.64%, 2.98%, 3.60%, 5.09% and 3.09%, respectively. In the process of selection and optimization of the chromatographic conditions, we observed the importance of metal ions to discretion, and discussed the temperature, pH of the buffer solution and dosage of dansyl chloride in derivation. Under the above conditions, the reaction was perfect, and the baseline of the detected materials thoroughly separated.</p><p><b>CONCLUSION</b>The method to detect monoamine neurotransmitters and its metabolites by HPLC and pre-column derivatization with dansyl chloride was established; and this method could provide reference for the detection of polyamine by HPLC.</p>

O papel do polimorfismo funcional VNTR da região promotora do gene MAOA nos transtornos psiquiátricos / The role of the VNTR functional polymorphism of the promoter region of the MAOA gene on psychiatric disorders

INTRODUÇÃO: Muitos estudos têm investigado a associação do polimorfismo VNTR (número variável de repetições em série) localizado na região promotora do gene da enzima monoamina oxidase A (MAOA) com alterações no comportamento humano e em diversos transtornos psiquiátricos. OBJETIVO: O objetivo do presente trabalho foi revisar a literatura sobre a participação desse polimorfismo funcional na modulação do comportamento humano para o desenvolvimento dos transtornos psiquiátricos. MÉTODO: A pesquisa foi realizada na literatura em inglês, de janeiro de 1998 a junho de 2009, disponível no Medline, Embase, Web of Science e na base de dados PsycInfo, utilizando os seguintes termos: "MAOA e comportamento humano" e "MAOA e psiquiatria". RESULTADOS: Foram encontrados 3.873 estudos. Desses, 109 foram selecionados e incluídos na revisão. Encontrou-se associação de alelos de baixa atividade do VNTR com transtorno de personalidade antissocial, transtorno de conduta, transtorno de déficit de atenção e hiperatividade, jogo patológico e dependência de substâncias. Alelos da alta atividade da MAOA foram associados a depressão, ansiedade, neuroticismo e anorexia nervosa. Não se encontrou associação entre polimorfismos da MAOA e esquizofrenia e transtorno bipolar. CONCLUSÃO: Os principais achados dão suporte ao papel do polimorfismo VNTR da região promotora do gene da MAOA em alguns transtornos psiquiátricos, apesar das divergências encontradas devidas às dificuldades metodológicas de estudos em genética. De modo geral, os estudos associam os alelos de baixa atividade da MAOA com comportamentos impulsivos e agressivos ("comportamentos hiperativos"), enquanto os alelos de alta atividade do gene são mais associados a "comportamentos hipoativos".

INTRODUCTION: A functional variable number of tandem repeats (VNTR) polymorphism of the promoter region of the monoamine oxidase A (MAOA) gene has been described and many studies have investigated the association of this polymorphism with human behaviors, as well as with several psychiatric disorders. OBJECTIVE: This study aimed to review the literature on the role of the VNTR functional polymorphism of the promoter region of the MAOA gene on the modulation of human behavior for the development of psychiatric disorders. METHOD: Searches on the Medline, Embase, Web of Science and PsycInfo databases were performed including works from January 1998 to June 2009. The words used were: "MAOA and human behavior" and "MAOA and psychiatry". RESULTS: Several studies were found (N = 3,873). After the selection process, 109 papers were included in the review. There was found an association of MAOA low activity alleles with antisocial personality disorder, conduct disorder, ADHD, pathological gambling, and substance abuse. High activity alleles were associated with neuroticism, anorexia nervosa and depression and anxiety disorders. There was no association between the MAOA polymorphisms and bipolar disorder and schizophrenia. DISCUSSION: The main findings, summarized in this paper, support a role of MAOA VNTR polymorphism in some psychiatric disorders although some divergences were found due to methodological difficulties in genetic studies. In general, the studies associated the low activity alleles with impulsivity and aggressive behavior ("hyperactive behaviors"), and the high activity alleles of the gene with "hypoactive behaviors", such as depression and anxiety, which demonstrates a modulation of the MAOA enzyme in "hyperactive" and "hypoactive" disorders.

Effects of apomorphine on locomotive activity and monoamine metabolism: a dose related study

We have monitored dose dependent effects of apomorphine on motor activity and monoamine metabolism. Behavioral sensitization and craving, which develop upon repeated treatment with dopamine receptor agonist apomorphine, are major limitations of the therapeutic use of apomorphine in Parkinson's patients. Effects of single [intraperitoneal] injection of apomorphine at different doses [i.e., 1.0, 2.0 and 4.0 mg/kg] on exploration in a novel environment [open field] and locomotion in a familiar environment [home cage] were investigated. Results show significantly enhanced activity in home cage [monitored 5min post injection] in a dose dependent manner. However, no significant influence of apomorphine on exploration of open field was observed in the present study [monitored 15min and 40min post injection]. Animals were decapitated 1 hr post apomorphine injection and whole brains of animals were collected and stored at -70°C. Biogenic amines [i.e., 5-Hydroxytryptamine and dopamine] and metabolites [i.e., Dihydroxyphenylacetic acid, Homovanillic acid and 5-Hydroxyindoleacetic acid] were estimated by reverse phase High Performance Liquid Chromatography with electrochemical detector [HPLC-EC]. Effect of low [l.0mg/kg] dose of apomorphine was found to be nonsignificant on 5-Hydroxytryptamine [5-HT], 5-Hydroxyindoleacetic acid [5-HIAA] and dopamine [DA] levels. Moderate [2.0 mg/kg] dose of drug increased [p<0.05] levels of Homovanillic acid [HVA]. Whereas, high [4.0 mg/kg] dose of apomorphine decreased Dihydroxyphenylacetic acid [DOPAC] levels. Results could be helpful in elucidating the effect of apomorphine at different doses and its implication for extending therapeutics in Parkinson's and related disorders

Effects of Chinese herbal compound on monoamine and neuronal amino acids in rat's telencephalon in the course of exhaustion and recovery process / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effect of Chinese herbal compound on variance of neurotransmitters in rat telencephalon and to further discuss the mechanism underlying Chinese herbal compound in improving exercise capacity and promoting recovery from exercise-induced fatigue.</p><p><b>METHODS</b>64 rats (8 week old) were randomly divided into medicine group (MG) and control group (CG). Chinese herbal compound was administered to rats of MG for 8 weeks. 8 weeks later, every group was divided into 4 subgroups and all were killed at different time point separately, and then neurotransmitter in rat brain was tested.</p><p><b>RESULTS</b>The exhaustion time of MG was significantly longer than that in CG (P < 0.01). In rest conditions, glutamic acid (GLU) of MG was significantly higher than that in CG (P < 0.01), while, there were no significant differences between MG and CG in other indexes. After fixed quantitative load exercise, the content of 5-hydroxytryptamineZZ(5-HT), 5-hydroindole acetic (5-HIAA), gamma-aminobutyric acid (GABA), Dopamine (DA) and 5-HT/5-HIAA were significantly lower than those in CG, while, GLU, GLU/GABA and DA/5-HT were significantly higher than those in CG. Compared with CG, exhaustion significantly (P < 0.05) decreased 5-HT, GABA and 5-HT/5-HIAA, and significantly (P<0.05) increased GLU, DA/5-HT and GLU/GABA level in MG. 12 h after exhaustion, in contrast to CG, level of 5-HT and 5-HT/5-HIAA in MG were significantly (P < 0.01) lower while GLU, DA, GABA and DA/5-HT were significantly (P < 0.01) higher.</p><p><b>CONCLUSION</b>During exhaustion exercise, Chinese herbal compound demonstrated strong inhibiting effect on synthesis of 5-HT, 5-HIAA, DA, GABA and promoting effect on GLU synthesis, this had been confirmed by the combined effect, including increase of excitatory transmitter and excitability of central nervous system and the prolongation of exhaustion time and promoting recovery from fatigue.</p>

Alterations on monoamines concentration in rat hippocampus produced by lipoic acid / Alterações na concentração de monoaminas no hipocampo de ratos produzidas pelo ácido lipóico

The purposes of the present study were to verify monoamines (dopamine (DA), norepinephrine (NE), serotonin (5-HT)), and their metabolites (3,4-hydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA)) contents in rat hippocampus after lipoic acid (LA) administration. Wistar rats were treated with 0.9 percent saline (i.p., control group) and LA (10, 20 or 30 mg/kg, i.p., LA10, LA20 and LA30 groups, respectively). After the treatments all groups were observed for 24 h. The NE and DA levels were increased only in 20 mg/kg dose of LA in rat hippocampus. Serotonin content and in their metabolite 5-HIAA levels was decreased in same dose of LA. On the other hand, in DOPAC and HVA levels did not show any significant change. The alterations in hippocampal monoamines can be suggested as a possible of brain mechanism of action from this antioxidant. The outcome of the study may have therapeutic implications in the treatment of neurodegenerative diseases.

O objetivo do presente estudo foi verificar a concentração das monoaminas (dopamina (DA), norepinefrina (NA), serotonina (5-HT)), e seus metabólitos (ácido 3,4-hidroxifenil (DOPAC), ácido homovanílico (HVA) e 5 ácido hydroxiindolacético (5-HIAA)) no hipocampo de ratos após administração do ácido lipóico (AL). Ratos Wistar foram tratados com solução salina 0,9 por cento (i.p., grupo controle) e AL (10, 20 ou 30 mg/kg, i.p., AL10, AL20 e AL30 grupos, respectivamente). Após os tratamentos todos os grupos foram observados durante 24 h. O conteúdo de DA no hipocampo de ratos foi aumentado apenas com AL na dose de 20 mg/kg dose. A concentração de serotonina e do seu metabólito 5-HIAA também foi diminuída com esta dose de AL. Por outro lado, os níveis de DOPAC e de HVA não mostrram nenhuma mudança significativa. As alterações na concentração das monoaminas hipocampais podem ser sugeridas como um possível mecanismo de ação cerebral deste antioxidante. O resultado do estudo pode ter implicações terapêuticas no tratamento de doenças neurodegenerativas.

Research traditional Chinese medicine properties by detecting rats' monoamine neurotransmitter after given two different traditional Chinese medicine / 中国中药杂志

<p><b>OBJECTIVE</b>To find out the essence of the traditional Chinese medicine properties from detecting the rats' monoamine neurotransmitter after given different traditional Chinese drug.</p><p><b>METHOD</b>The property of rhizome curcumae and radix curcumae is opposite, they were given to rats respectively for one month. Next, HPLC-ECD method was used to detect the rats' monoamine neurotransmitter in different encephalic region.</p><p><b>RESULT</b>Rhizome curcumae can raise the rats' monoamine neurotransmitter, but radix curcumae inhibits the rats' monoamine neurotransmitter.</p><p><b>CONCLUSION</b>There are correlations between the traditional Chinese medicine properties and monoamine neurotransmitter.</p>

Effect of environment temperature on the recovery of microdialysis probe for monoamine neurotransmitter / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of environment temperature on the recovery of microdialysis probe for neurotransmitters.</p><p><b>METHODS</b>Neurotransmitters NE, DA, and 5-HT were dialyzed with 4 mm membrane length microdialysis probes in different environmental temperature. There were three conditions: lower temperature condition, the temperature of standard solution and that of the perfusate were both 24 degree; higher temperature condition,both were 37.5 degree; and the middle temperature:the perfusate was 24 degree and the standard solution was 37.5 degree. The concentrations of neurotransmitters in the dialyzed solution and the standard solution were analyzed by HPLC-ECD, and recoveries were then calculated.</p><p><b>RESULT</b>In lower temperature condition,the recoveries of microdialysis probe for NE, DA, 5-HT were 18.3 %, 19.6% and 16.9%, respectively. In middle temperature condition, the recoveries were 29.6%, 30.7% and 24.3%, respectively, and in higher temperature condition, those were 49.2%, 47.5% and 37.2%, respectively. With the analysis of variance, the recoveries for NE, DA, 5-HT increased with temperature significantly (P<0.01).</p><p><b>CONCLUSION</b>Both the perfusate and the standard solution affects the environmental temperature of microdialysis probe, which in turns affects the recovery of microdialysis probe for neurotransmitters. So in order to calculate the recovery more accurately, the standard solution/the perfusate should be kept in body temperature.</p>

Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer's disease & protection by Moringa oleifera.

BACKGROUND & OBJECTIVES: The monoaminergic systems which exert a modulatory role in memory processing, are disturbed in Alzheimer's disease (AD) and Moringa oleifera (MO) has been shown to exert its effect in CNS by altering the brain monoamines. The present study aims to see whether chronic oral treatment of ethanolic extract of MO leaves can alter the brain monoamines (norepinephrine, dopamine and serotonin) in distinct areas of brain in rat model of AD caused by intracerebroverticle (ICV) infusion of colchicine and hence can provide protection against monoaminergic deficits associated with AD. METHODS: Rats were given ICV infusion of colchicine (15 microg/5microl) and MO leaf alcoholic extract was given in various doses. The effective dose was standardized by radial arm maze (RAM) training. From the selected dose of 250 mg/kg body weight, the biochemical estimations and EEG studies were performed. RESULTS: Stereotaxic ICV infusion of colchicine significantly impaired the RAM performance together with decrease in norepinephrine (NE) level in cerebral cortex (CC), hippocampus (HC) and caudate nucleus (CN). Dopamine (DA) and serotonin (5-HT) levels were decreased in CC, HC and CN. The EEG studies showed a decrease in beta and alpha waves and increase in biphasic spike wave pattern in experimental Alzheimer rat model. Treatment with MO extract markedly increased the number of correct choices in a RAM task with variable alteration of brain monoamines. The EEG studies showed an increase in beta waves and a decrease in spike wave discharges. INTERPRETATION & CONCLUSION: Our results showed that brain monoamines were altered discreetly in different brain areas after colchicine infusion in brain. After treatment with MO, leaf extract the monoamine levels of brain regions were restored to near control levels. Our findings indicated that MO might have a role in providing protection against AD in rat model by altering brain menoamine levels and electrical activity.

CNS depressive role of aqueous extract of Spinacia oleracea L. leaves in adult male albino rats.

Treatment with Spinacia oleracea extract (SO; 400 mg/kg body weight) decreased the locomotor activity, grip strength, increased pentobarbitone induced sleeping time and also markedly altered pentylenetetrazole induced seizure status in Holtzman strain adult male albino rats. SO increased serotonin level and decreased both norepinephrine and dopamine levels in cerebral cortex, cerebellum, caudate nucleus, midbrain and pons and medulla. Result suggests that SO exerts its CNS depressive effect in PTZ induced seizure by modulating the monoamines in different brain areas.

Influence of isotretinoin treatment on monoamines in different brain areas of male rats

Despite widespread use of isotretinoin for its anti-acne effects and its current evaluation in clinical trials as a cancer treatment, little is known about its effect on brain function and neuronal pathways in adult animals, particularly after oral administration which mimics the human route. Here, adult male rats were gavaged daily with olive oil and 1.5mg/kg/day isotretinoin for 4 weeks during which body weight was measured and changes in food intake and locomotor activity were observed. After decapitation, the concentrations of dopamine [DA], norepinephrine [NE], serotonin [5-HT] and 5-hydroxyindoleacetic acid [5-HIAA] were measured in different brain areas of rats after 2 and 4 weeks of repeated injection. The results show that, following isotretinoin administration body weight, food intake and locomotor activity were generally decreased. Treatment with isotretinoin produced marked increases in the concentrations of DA and 5-HIAA after 2 and 4 weeks and of NE after 4 weeks in the various brain regions examined. However, level of 5-HT was significantly decreased in most of the brain areas studied after 2 and 4 weeks following isotretinoin treatment. The results also show that all of these effects induced by isotretinoin treatment were tended to resolve within one week of drug cessation. It is possible to conclude that such alteration in monoamine systems could contribute to the isotretinoin induced increase in depression related behavior