Effects of (−)-Sesamin on Memory Deficits in MPTP-lesioned Mouse Model of Parkinson's Disease

This study investigated the effects of (−)-sesamin on memory deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD). MPTP lesion (30 mg/kg/day, 5 days) in mice showed memory deficits including habit learning memory and spatial memory. However, treatment with (−)-sesamin (25 and 50 mg/kg) for 21 days ameliorated memory deficits in MPTP-lesioned mouse model of PD: (−)-sesamin at both doses improved decreases in the retention latency time of the passive avoidance test and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid, improved the decreased transfer latency time of the elevated plus-maze test, reduced the increased expression of N-methyl-D-aspartate (NMDA) receptor, and increased the reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB). These results suggest that (−)-sesamin has protective effects on both habit learning memory and spatial memory deficits via the dopaminergic neurons and NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mouse model of PD, respectively. Therefore, (−)-sesamin may serve as an adjuvant phytonutrient for memory deficits in PD patients.

Effects of Gypenosides on Dopaminergic Neuronal Cell Death in 6-Hydroxydopamine-lesioned Rat Model of Parkinson's Disease with Long-term L-DOPA Treatment

The goal of this study was to determine whether gypenosides (GPS) exert protective effects against dopaminergic neuronal cell death in a 6-hydroxydopamine (OHDA)-lesioned rat model of Parkinson's disease (PD) with or without long-term 3,4-dihydroxyphenylalanine (L-DOPA) treatment. Rats were injected with 6-OHDA in the substantia nigra to induce PD-like symptoms; 14 days after injection, groups of 6-OHDA-lesioned animals were treated for 21 days with GPS (25 or 50 mg/kg) and/or L-DOPA (20 mg/kg). Dopaminergic neuronal cell death was assessed by counting tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra and measuring levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. Dopaminergic neuronal cell death induced by 6-OHDA lesions was ameliorated by GPS treatment (50 mg/kg). L-DOPA treatment exacerbated 6-OHDA-induced dopaminergic neuronal cell death; however, these effects were partially reversed by GPS treatment (25 and 50 mg/kg). These results suggest that GPS treatment is protective against dopaminergic neuronal cell death in a 6-OHDA-lesioned rat model of PD with long-term L-DOPA treatment. Therefore, GPS may be useful as a phytotherapeutic agent for the treatment of PD.

Therapeutic effect of a natural squamosamide derivative FLZ on Parkinson's disease model mice induced by LPS plus MPTP / 药学学报

The aim of this study is to investigate the protective effect of N-[2-(4-hydroxyphenyl)ethyl]-2-(2, 5-dimethoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl)acrylamide (FLZ), a novel synthetic squamosamide cyclic derivative, against Parkinson's disease (PD) model mice induced by the inflammatory bacterial endotoxin, lipopolysaccharides (LPS) and the neurotoxin 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). C57/BL mice were ip injected LPS (5 mg x kg(-1)) once. One week following the LPS injection, mice received a subcutaneous injection of MPTP (25 mg x kg(-1)) once daily for 2 days. Eight weeks later, FLZ (25, 50 and 75 mg x kg(-1)) was orally administered to mice once daily for 60 days. The motor ability of the mice was evaluated by rod climbing test and footprint test. The dopamine (DA) levels in mouse striatum were determined by high performance liquid chromatography system. The tyrosine hydroxylase (TH)-positive cells were showed by immunohistochemical analysis. FLZ treatment significantly improved motor dysfunction of mice challenged by LPS plus MPTP. The increase of TH-positive cell numbers and elevation of DA levels may be contributed to the beneficial effects of FLZ on motor behavior. This study showed FLZ has significant therapeutic effect on LPS plus MPTP induced chronic PD model, which indicates its potential as a new candidate drug to treat PD.

Extracción de metabolitos ácidos durante el análisis de catecolaminas en tejido cerebral de ratas / Extraction of acid metabolites during the analysis of catecholamines in rat brain tissue / Extração de metabólitos ácidos durante a análise de catecolaminas no tecido cérebro de rato

A través del método de equilibrio batch se comparó la adsorción de las catecolaminas Dopamina (DA), Noradrenalina (NA) y Adrenalina (A), y de los metabolitos ácido dihidroxifenilacético (Dopac) y ácido indolacético (5- HIAA) en las fases sólidas octadecil (C18) hidrofóbica, diol (C Diol) hidrofílica y de intercambio catiónico débil (WCX). En la fase sólida WCX a pH 4,0 se observó un 78% de adsorción de catecolaminas y 68% de adsorción de Dopac. Las isotermas de adsorción de las catecolaminas en la fase WCX son de tipo Langmuir. La adrenalina tiene mayor afinidad que la dopamina por la fase WCX a pH 4,0 y la dopamina mayor afinidad que el Dopac y éste es coadsorbido sobre las catecolaminas adsorbidas en la fase WCX. Un ensayo con solventes orgánicos demostró que el tolueno extrajo selectivamente de una mezcla sintética el Dopac y el 5-HIAA coadsorbido, mientras que en una muestra de tejido cerebral de ratas experimentales fueron extraídos el Dopac y el ácido homovanílico (HVA). Estos resultados sirvieron para proponer un paso adicional de extracción con solventes orgánicos para la separación de metabolitos ácidos durante la extracción en fase sólida (EFS) en el análisis de catecolaminas.

The adsorptions of Dopamine (DA), Noradrenaline (NA), and Adrenaline (A) catecholamines were compared by using the batch equilibrium method, as well as those of the dihydroxyphenylacetic acid (Dopac) and indolacetic acid (5-HIAA) metabolites on the hydrophobic octadecyl (C18), hydrophilic diol (C Diol) and weak cation exchange (WCX) solid phases. On the WCX solid phase at pH 4.0, catecholamines adsorption of 78% and Dopac adsorption of 68% were observed. The adsorption isotherms of catecholamines on the for the WCX phase at pH 4.0 than dopamine, dopamine has greater affinity than Dopac, and this latter is coadsorbed over the adsorbed catecholamines on the WCX phase. A trial with organic solvents demonstrated that toluene selectively extracted Dopac and the coadsorbed 5-HIAA from a synthetic mix, while in a brain tissue specimen from experimental rats, Dopac and homovanilic acid (HVA) were extracted. These results served to propose an additional extraction step with organic solvents throughout the separation of acid metabolites during solid phase extraction (EFS) for the analysis of catecholamines.

Effect and mechanism on dopamine contents of striatum in rat model of Parkinson's disease ginsenoside Rg1 / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate effect and mechanisms on dopamine contents of striatum (Str) in the 6-OHDA induced rat model of Parkinson's disease (PD) by ginsenoside Rg1.</p><p><b>METHOD</b>Ovariectomized PD rats were treated with vehicle, ginsenoside Rg1, (10 mg x kg(-1)) or estrogen receptor (ER) antagonist ICI 182,780 for 14 d. The change of apomorphine-linduced rotational behavior in PD rats were observed. The high performance lipid chromotophotography (HPLC) was used to determine the contents of DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)in striatum.</p><p><b>RESULT</b>Rg1 treatment could ameliorate the PD rat's rotational behavior induced by apomorphine (P < 0.01). This effect could be blocked by ER antagonist ICI 182,780. The DA, DOPAC and HVA levels in the injured side of Str for PD rats were significantly decreased compared with the intact side (P < 0.01). Rg1, treatment could increase DA contents in the injured side of Str (P < 0.01). ICI 182,780 could completely block the neuroprotective effects of Rg1. The DA contents and its metabolites in the injured side of the ICI treatment group were significantly decreased compared with the Rg1 group (P < 0.01).</p><p><b>CONCLUSION</b>Ginsenoside Rg1 may have protective effects on the dopaminergic neurons for the 6-OHDA induced OVX rat model of PD, ER. May be involved in the protection action.</p>

Tyrosine hydroxylase as a target for deltamethrin in the nigrostriatal dopaminergic pathway / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the effects of deltamethrin on tyrosine hydroxylase in nigrostriatum of male rats.</p><p><b>METHODS</b>Sprague-Dawley rats were daily treated with deltamethrin at 6.25 or 12.5 mg/kg body weight by gavage for 10 days. Then HPLC-fluorescence detection was used to analyze the contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homoranillic acid (HVA) in substantial nigra and striatum. The activities of tyrosine hydroxylase (TH) were also detected by HPLC-fluorescence detection. TH mRNA or TH protein levels were measured by RT-PCR and immunohistochemistry method.</p><p><b>RESULTS</b>The content of DA in striatum was significantly decreased by the treatments, suggesting an inhibition of DA synthesis by deltamethrin. The contents of DA metabolites DOPAC and HVA increased, indicating increased dopamine turnover. Furthermore, deltamethrin significantly decreased the activity, as well as the mRNA and protein levels of TH.</p><p><b>CONCLUSIONS</b>These findings reveal a novel aspect of deltamethrin neurotoxicity and suggest tyrosine hydroxylase as a molecular target of deltamethin on dopamine metabolism in the nigrostriatal pathway.</p>

Effect of dimethoate on serum monoamines neurotransmitters in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the effect of dimethoate on the monoamine Neurotransmitters, including norepinephrine (NE), epinephrine (E), serotonin (5-HT), dopamine (DA) and its metabolite (3, 4-hydroxyphenylacetic acid, DOPAC) in the serum of rats and furthermore to explore the non-cholinergic mechanism of organophosphate induced toxicity.</p><p><b>METHODS</b>Groups of rats were treated with saline and 38.9, 83.7 and 180 mg/kg dimethoate respectively and were decapitated at the different time course from 0.5 to 24 hours after the administration. The monoamines neurotransmitters were determined by the reverse-phase high-performance liquid chromatography with the electrochemical detection.</p><p><b>RESULTS</b>The serum concentrations of DA (8.42% - 248.42% of the control), DOPAC (17.22% - 68.21% of the control) increased, according with the DM dosage and the exposure time, while the levels of NE (9.65% - 38.26% of the control) and E (11.00% - 32.62% of the control) contents decreased at the same time.</p><p><b>CONCLUSION</b>These findings indicate that dimethoate induced toxic effects can alter the monoamine levels at the different dosage and the time exposure in the serum of rats. It suggests that some non-cholinergic mechanisms may be involved in the dimethoate intoxication.</p>

Effects of Guanyu capsule on the behavior and cerebral cortex monoamine neurotransmitters in depressive model of olfactory bulb damage rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the behavioral changes and the levels of monoamine neurotransmitters in the anterior cortex in the olfactory bulb damage rats after being treated with Guanyu capsules (GYC).</p><p><b>METHOD</b>Open-field test and step-down passive avoidance test were used to observe the behavior in model rats. HPLC-ECD was used to analyze the influences of GYC on the levels of monoamine neurotransmitters.</p><p><b>RESULT</b>In the model rats, there was a characteristic hyperactivity in the Open-field and learning deficits in step-down passive avoidance (P < 0.01). The contents of 5-HT reduced, and the rate of DOPAC/DA increased significantly (P < 0.01). GYC 1.2, 0.6 g x kg(-1) could correct behavioral changes increase the contents of 5-HT, and decrease DOPAC/DA level (P < 0.01).</p><p><b>CONCLUSION</b>GYC can correct behavioral changes in rats model of olfactory bulb damage, and regulating 5-HT and DA metabolism in cortex is one of the antidepressive mechanisms of GYC.</p>

Effects of Tianzhi Keli on extracellular acetylcholine and catecholamine levels in striatum of rats with neuromitochondrial impairment / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effects of Tianzhi Keli (TZ) on acetylcholine (ACh) and catecholamine levels in striatum of rats with neuromitochondrial impairment, and try to find out the neuroprotective mechanism of TZ.</p><p><b>METHOD</b>The microdialysis and high performance liquid chromatography (HPLC)-post column Immobilized enzyme reactor (IMER)-electrochemical detection (ED) were used to establish a model of mitochondrial energy metabolism impairment which induced by perfusion with sodium azide (NaN3), and measure continuously the effects of TZ on extracellular ACh, choline (Ch) and catecholamine of model rats.</p><p><b>RESULT</b>After perfusion with NaN3, ACh, noradrenalin (NE), adrenaline (E), dopamine (DA), 3,4-Dihydroxyphenyl-aletic (DOPAC), and homovanillic acid (HVA) levels were decreased obviously (P < 0.05-0.01), while Ch level was increased distinctly (P < 0.01). Transmitters levels were recovered individually after stop the perfusion with NaN3. TZ can postpone the decrease of ACh and advance the recover of Ch. The effect of TZ coupled with duxil on increasing ACh level is more obviously than effect of TZ or duxil. TZ is also showing a tendency to postpone the decrease of catecholamine and advance its recovery. TZ coupled with duxil can advance the recovery of DOPAC and adjust the metabolic abnormity positively.</p><p><b>CONCLUSION</b>TZ has effect on protecting impairment of choline neurosystem, which induced by damage of mitochondrion and abnormity of energy metabolism; coupled with duxil have synergistic action. TZ also has tendency to protect the impairment of epinephrine and dopamine neurosystem.</p>

Effects of Chronic Alcohol Exposure on Dopaminergic and Serotonergic Neurotransmission System in Rat / 대한정신약물학회지

OBJECTIVE: This study investigates the effects of chronic alcohol exposure on rat brain THmRNA expression, TH (tyrosine hydroxylase) acitivity, and TPH (tryptophan hydroxylase) activity which are important in synthesis of dopamine and serotonin and other components of both the dopaminergic and serotonergic systems of the rat brain. METHODS: Rats were fed a liquid diet containing alcohol for 4 weeks. We investigated effects of chronic alcohol exposure on dopaminergic systems as follows. We evaluated expression of THmRNA in LC, VTA and substantia nigra by using in-situ hybridization and measured activity of TH by using immunoassay. We used HPLC for simultaneous measurement of dopamine, DOPAC and HVA in the cerebral cortex, striatum, hypothalamus, hippocampus, mid brain, hind brain, and cerebellum. Also we investigated serotonergic systems as follows. We evaluated expression of TH mRNA in the dorsal raphe nucleus by using radioprobe and measured the activity of TPH by using enzyme immunoassay. We used HPLC for simultaneous measurement of 5-HT and 5-HIAA in the cerebral cortex, striatum, hypothalamus, hippocampus, mid brain, hind brain, and cerebellum. RESULTS: Alcohol exposure for 4 weeks increased the expression of TH mRNA in the ventral tegmental area and the locus ceruleus but not in the substantia nigra. The 4 weeks of alcohol exposure did not cause significant changes in levels of dopamine and metabolites in the different areas of the brain, nor was it associated with changes in the maximal binding and affinity (Kd) of anterior striatal dopamine D2 receptor. Alcohol exposure for 4 weeks had no effect on the expression of TPH mRNA or on the activity of TPH in the dorsal raphe nucleus and the hypothalamus. CONCLUSION: We reported at first that chronic alcohol exposure could increase TH mRNA in the locus ceruleus. In a previous study of acute alcohol treatment, there is increase of dopamine metabolism but in this study, we did not observe any changes in dopamine metabolism in the different areas of the brain. Also we did not see any significant changes in the synthesis and metabolism of serotonin after 4 weeks of chronic alcohol exposure compared with control. Therefore, synthesis and metabolism of serotonin was affected in the acute phase. And, as previous reports have suggested, any changes caused by alcohol returned to previous levels via adaptation and regulatory mechanisms.

Effects of pyrethroids on dopamine and its metabolites in nigrostriatum of male rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of pyrethroids on nigrostriatal dopaminergic pathways in male rats and its mechanism.</p><p><b>METHODS</b>Different doses of permethrin (PM, 200, 400 mg/kg) and deltamethrin (DM, 6.25, 12.50 mg/kg) in corn oil were administered to rats by gavage once daily for ten days, then the contents of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the substantial nigra and striatum were analyzed by HPLC-fluorescence detection.</p><p><b>RESULTS</b>The contents of DA in striatum in four administered groups were decreased to a certain extent. DA in 6.25 mg/kg DM group [(6.14 +/- 0.57) microg/g wet weight] was lower than that in control group [(9.46 +/- 1.95) microg/g wet weight], P < 0.05. The turnover rate of DA in 200, 400 mg/kg PM and 6.25, 12.5 mg/kg DM groups increased by 133.33%, 166.67%, 166.67%, 266.67% respectively (P < 0.05 or P < 0.01), however there was no significant difference in DA and DOPAC in substantial nigra between control and administered groups.</p><p><b>CONCLUSION</b>DM may inhibit tyrosine hydroxylase and decrease the level of DA in striatum, and both pyrethroid pesticides may increase the metabolism of dopamine in striatum.</p>

Monoaminergic Activity by Drugs Acting on Adrenergic alpha2-receptors in Rat Hippocampus and Primary Visual Cortex / 대한정신약물학회지

OBJECTIVE: The aim of the this study was to compare the effects of clonidine (a alpha2-adrenoceptor and imidazoline receptor agonist), yohimbine (a selective alpha2-adrenoceptor antagonist) and idazoxan (a alpha2-adrenoceptor and imidazoline receptor antagonist) on extracellular monoamines and their metabolites by using the awakening animal microdialysis and high-performance liquid chromatography with electrochemical detection (HPLC-ECD) in brain regions, which are suggested to have regulatory role in depression. METHODS: We used intracerebral microdialysis in awakening rats by inserting probe through the dorsal hippocampus and occipital cortex especially in primary visual cortex, We studied respective effects of 2.0 mg/kg of clonidine, 5.0 mg/kg of yohimbine, and 5.0 mg/kg of idazoxan on the release of MHPG (a major metabolite of norepinephrine), norepinephrine (NE), DOPAC (a major metabolite of dopamine), and 5-HIAA (a main metabolite of serotonin) by intraperitoneal administration. RESULTS: Clonidine decreased the release of MHPG, NE, DOPAC, and 5-HIAA in both dorsal hippocampus and occipital cortex regions, and there were no significant differences in releasing pattern of all monoamines and their metabolites. Both yohimbine and idazoxan enhanced the release of MHPG, NE, DOPAC, and 5-HIAA in both brain regions, but there were significant differences in releasing pattern of NE and 5-HIAA. Idazoxan induced the delayed and higher efflux of NE and 5-HIAA in the primary visual cortex than yohimbine, but not in the hippocampus. CONCLUSION: This study shows that the selective alpha2-adrenoceptor antagonists increase basal monoamine output and enhance the metabolism of them in the hippocampus and primary visual cortex, and the imidazoline receptor has modulatory role in the regulation of monoamine release in primary visual cortex than hippocampus. It also suggests that high turnover rate of serotonin and norepinephrine in primary visual cortex may contribute to the pathophysiological role in depression.

Genetic, biochemical, and characterization of neurological mutant 3, a new mouse model for Parkinson's disease

We have identified a new mutant mouse that we have named new mouse neurological mutant 3 (NM3); it may be a useful model to understand the underlying molecular and genetic basis of Parkinson's disease (PD). A mouse carrying the NM3 mutation arose spontaneously in an RIIIS/J breeding colony and was identified as having a movement disorder. Upon neurological examination of these mice, their movement was found to be slow and abnormal, with characteristic choreaform and bradykinetic-type movements, typical of PD. The importance of the gene mutation in NM3 in the molecular pathway involved in this pathology is underscored by the fact that these mice do not survive past weaning age if they are homozygous for the genetic mutation. We localized the gene mutation by positional cloning and genetic mapping to mouse chromosome 2 in an area that corresponds to human chromosome 2q24-31, which does not contain any known genes associated with PD. However, there was a significant decrease of 15-20 in the levels of dopamine, and its principal metabolite, 3,4-dihydroxyphenylacetic acid, in the midbrain of affected mice. Low concentrations of these substances are associated with PD in human patients, making these mutant mice candidates for studies of this disease

Alterações agudas dos níveis de neurotransmissores em corpo estriado de ratos jovens após estado epiléptico induzido por pilocarpina / Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus

Altas doses de agonista colinérgico muscarínico, pilocarpina, produzem alterações comportamentais, convulsöes e estado epiléptico em ratos. O objetivo desse estudo foi verificar as alterações nas concentrações dos neurotransmissores em corpo estriado de ratos em desenvolvimento após estado epiléptico induzido pela pilocarpina. Ratas Wistar foram tratadas com uma única dose de pilocarpina (400mg/Kg; s.c.). Controles receberam salina. A concentraçäo dos neurotransmissores foi determinada através do HPLC, no corpo estriado de ratos que no período de observaçäo de 1 e 24h desencadearam estado epiléptico e näo sobreviveram à fase aguda do quadro convulsivo. Foi observada reduçäo nos níveis de dopamina, serotonina, ácido dihidroxifenilacético, ácido 5-hidroxiindolacético, e aumento no ácido 4-hidroxi-3-metoxi-fenilacético. Os resultados mostraram que a ativaçäo do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo

Effect of Hypoxia-Ischemia on Striatal Monoamine Metabolism in Neonatal Rat Brains

PURPOSE: We intended to evaluate the effect of hypoxia-ischemia on extracellular striatal monoamine metabolism in neonatal rat brains by in vivo microdialysis. METHODS: The right common carotid arteries of five or six-day old rats were surgically ligated, and the probes for microdialysis were inserted into the right striatum with stereotaxic instrument. After stabilization for two hours, artificial cerebrospinal fluid was infused via the probe for microdialysis and samples were collected during hypoxia-ischemia and recovery periods at 20 minute intervals. The concentrations of DA(dopamine), DOPAC(3,4-di-hydroxyphenyl acetic acid), HVA(homovanillic acid), NE(norepinephrine), and 5-HIAA(5-hydroxy indoleacetic acid) were measured by HPLC(high performance liquid chromatography) and the changes were analysed. RESULTS: The striatal levels of dopamine metabolites such as DOPAC and HVA, were significantly decreased during hypoxia-ischemia, and increased to their basal level during reoxygenation(P0.05). DOPAC showed the most remarkable decrease(23.0+/-4.2%, P<0.05), during hypoxia-ischemia and increase to the basal levels during reoxygenation(120.8+/-54.9%, P<0.05), and HVA showed the same pattern of changes as those of DOPAC during hypoxia-ischemia(35.3+/-7.6% of basal level, P<0.05) and reoxygenation (105.8+/-32.3%). However, the level of NE did not show significant changes during hypoxia-ischemia and reoxygenation. The levels of 5-HIAA decreased(74.9+/-3.1%) and increased(118.1+/-7.8%) during hypoxia-ischemia and reoxygenation, respectively(P<0.005). CONCLUSION: Hypoxia-ischemia had a significant influence on the metabolism of striatal monoamine in neonatal rat brains. These findings suggest that monoamine, especially dopamine, and its metabolites could have a significant role in the pathogenesis of hypoxic-ischemic injury of neonatal rat brains.

Characterization of Norepinephrine Release in Rat Posterior Hypothalamus Using in vivo Brain Microdialysis

In the present study, we used the microdialysis technique combined with high performance liquid chromatography (HPLC) and electrochemical detection to measure the extracellular levels of norepinephrine (NE) in the posterior hypothalamus in vivo, and to examine the effects of various drugs, affecting central noradrenergic transmission, on the extracellular concentration of NE in the posterior hypothalamus. Microdialysis probes were implanted stereotaxically into the posterior hypothalamus (coordinates: posterior 4.3 mm, lateral 0.5 mm, ventral 8 mm, relative to bregma and the brain surface, respectively) of rats, and dialysate collection began 2 hr after the implantation. The baseline level of monoamines in the dialysates were determined to be: NE 0.17 +/- 0.01, 3,4-dihydroxyphenylacetic acid (DOPAC) 0.94 +/- 0.07, homovanillic acid (HVA) 0.57 +/- 0.05 pmol/sample (n=8). When the posterior hypothalamus was perfused with 90 mM potassium, maximum 555% increase of NE output was observed. Concomitantly, this treatment significantly decreased the output of DOPAC and HVA by 35% and 28%, respectively. Local application of imipramine (50microM) enhanced the level of NE in the posterior hypothalamus (maximum 200%) compared to preperfusion control values. But, DOPAC and HVA outputs remained unchanged. Pargyline, an irreversible monoamine oxidase inhibitor, i.p. administered at a dose of 75 mg/kg, increased NE output (maximum 165%), while decreased DOPAC and HVA outputs (maximum 13 and 12%, respectively). These results indicate that NE in dialysate from the rat posterior hypothalamus were neuronal origin, and that manipulations which profoundly affected the levels of extracellular neurotransmitter had also effects on metabolite levels.

The effect of shourong compound formula on levels of dopamine and its metabolites in brain of Parkinson's disease mice induced by reserpine / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Shourong compound formula on treating Parkinson's disease.</p><p><b>METHOD</b>Parkinson's disease model mice induced by reserpine was used and by HPLC-ED the levels of Dopamine (DA) and its metabolites were determined.</p><p><b>RESULT</b>Madopar could increase the levels of DA in brain of PD mice. The effect of madopar together with Sourong compound formula was better than that of madopar(P < 0.001).</p><p><b>CONCLUSION</b>Shourong compound formula together with madopar has synergic effect on increase of DA level in brain and can reduce clinic dose of madopar so that side effect of madopar can be decreased.</p>

Effect of bromocriptine on 6-hydroxydopamine-induced lipid peroxidation and cytotoxicity in vitro and in vivo

The present study was to evaluate the protective effects of bromocriptine, which is known as D2 dopamine receptor agonist and used for the treatment of patients with Parkinson's disease (PD), on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro and in vivo. Lipid peroxidation product (malondialdehyde; MDA) produced by the administration of 6-OHDA was profoundly reduced following the treatment of bromocriptine in a dose-dependent manner in rabbit brain homogenate. Quinone formation by 6-OHDA autoxidation was also attenuated, and its effect was as potent as other antioxidants. Pretreatment of bromocriptine reduced the cytotoxicity of 6-OHDA on SH-SY5Y neuroblastoma cell lines dose-dependently. The loss of striatal dopamine and its metabolite, DOPAC (dihydroxyphenylacetic acid) as well as increase of MDA production caused by intrastriatal injection of 6-OHDA was significantly recovered following the treatment of bromocriptine. The present study clearly showed that bromocriptine had a protective action against 6-OHDA-induced neurotoxicity. These results suggest that bromocriptine has the antioxidant properties, which could be another advantage for delaying the progress of Parkinson's disease.

Study of dopamine transporter in the rat 6-hydroxydopamine Parkinson's disease model

BACKGROUND: Neuroprotective therapy is essential in the management of Parkinson's disease(PD). As symptomatic benefit of a treatment may clinically mask the disease progression, an evaluation of the effect of a neuroprotective therapy should be based on objective measurement of in vivo dopaminergic integrity: Nuclear imaging techniques such as SPECT or PET can visualize dopaminergic system using dopamine transporter ligands and show the promise for this purpose. The objective of this study is to examine the changes of dopamine transporter in the animal model of PD and those correlations with behavioral and biochemical changes. METHODS: We injected 6-hydroxydopamine into the substantia nigra in Sprague-Dawley rats to establish the unilateral PD model, and examined the rotation response after apomorphine injection as a behavioral aspect of the animal model. And we also measured the dopamine and DOPAC level in the striata and the dopamine transporter by [3H]-mazindol autoradiography. RESULTS: We observed that the rats showed turning behavior only after severe reduction of dopamine and DOPAC. There was a strong inverse correlation between rotation behavior and striatal dopamine, DOPAC and dopamine transporter density. There was a positive and strong linear-correlation between dopamine transporter density and dopamine or DOPAC levels. CONCLUSION: Measurement of dopamine transporter gives a good estimate of striatal dopamine level in an animal model of PD. In vivo measurement of dopamine transporter will give an objective information on the integrity of presynaptic nigrostriatal dopaminergic system.

Reduction of Central Dopamine Release in Hyperprolactinemia / 대한내분비학회지

Background: Prolactin(PRL) secretion is tonically inhibited by doparnine that originates from the hypothalamic tuberoinfundibular tract and reaches the lactotroph via the hypophyseal portal vessel. Hyperprolactinemia associated with oligomenorrhea-amenorrhea, galactorrhea and/or infertility is mainly due to PRL-secreting pituitary adenoma(PA). The diagnosis of idiopathic hyperprolac- tinemia(IHP) is made, when hyperprolactinemia is sustained and all causes of hyperprolactinemia are excluded without radiological abnormality. It is not known, whether IHP and PA are two distinct entities or two subsequent phases of the same disease. The etiology of both disorders remains unresolved. We investigated that PRL hypersecretion in patients with IHP and PA may be the result of a defect in the central nervous system(CNS)-dopamine release, and that there may be some differences in pathogenesis of both diseases. Methods: We measured 24 hour-urinary dopamine, norepinephrine, epinephrine, and serum and 24 hour-urinary VMA(vanillyl rnandelic acid), HVA(homovanilic acid), DOPAC(3,4-dihydroxy phenylaceticacid), MHPG(3-methoxy 4-hydroxy phenylglycol) in 10 normal controls, 9 patients with IHP, and 17 patients with PA in the early follicular phase. Results: Urinary HVA and DOPAC concentrations, the major metabolites of CNS dopaminergic activity, were signficantly lower in both patients with IHP and PA compared with those in normal controls(p 0.05), whereas they were not different in both disease groups. Dopamine, norepine-phrine, epinephrine, MHPG concentrations were similar to those of the normal controls. Although VMA concentrations of both disease groups were significantly higher than those of normal controls, all of them were within normal range. Conelusion: Although our data are unable to establish the precise biochemical defect responsible for central dopamine deficiency in pathogensis of IHP and PA, we can support the presence of a pathological reduction of brain dopamine activity in IHP and PA.