To investigate the effect of Rehmanniae Radix on depression-like behavior and monoamine neurotransmitters of chronic unpredictable mild stress(CUMS) model rats. CUMS combined with isolated feeding was used to induce the depression model of rats. The depression-like behavior of rats was evaluated by sucrose preference test, open field test, and forced swim test. Hematoxylin-Eosin(HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS) was used to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), 3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), norepinephrine(NE), and 3-methoxy-4-hydroxyphenyl glycol(MHPG) in rats. Western blot was used to detect the protein expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), and monoamine oxidase A(MAO-A) in the hippocampus of rats. Compared with the normal group, depressive-like behavior of rats was obvious in the model group. The arrangements of neurons in the CA1 and CA3 area of hippocampus were loose and disorderly. The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in the hippocampal area were decreased(P<0.01). The protein expression of TPH2 was decreased(P<0.01), but those of SERT and MAO-A were increased(P<0.01). In the Rehmanniae Radix groups with 1.8 g·kg~(-1) and 7.2 g·kg~(-1), the depression-like behavior of CUMS rats and pathological changes of neurons in CA1, CA3 area of hippocampus were improved. The protein expression of TPH2(P<0.05, P<0.01) was increased, and those of SERT and MAO-A were down-regulated(P<0.05, P<0.01). The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in hippocampus were increased(P<0.05, P<0.01). The changes in DA, DOPAC, HVA, DA/(DOPAC +HVA), NE, DHPG, and NE/DHPG were not statistically significant. The results suggested that Rehmanniae Radix improved depression-like behavior of CUMS rats, and the mechanism might be related to the regulation of synthesis, transportation, and metabolism of 5-HT neurotransmitter in the hippocampus.
3,4-Dihydroxyphenylacetic Acid/pharmacology* ; Animals ; Antidepressive Agents/therapeutic use* ; Chromatography, Liquid ; Depression/drug therapy* ; Disease Models, Animal ; Dopamine ; Eosine Yellowish-(YS)/pharmacology* ; Hematoxylin/pharmacology* ; Hippocampus/metabolism* ; Homovanillic Acid/pharmacology* ; Hydroxyindoleacetic Acid/metabolism* ; Methoxyhydroxyphenylglycol/pharmacology* ; Monoamine Oxidase/metabolism* ; Neurotransmitter Agents/metabolism* ; Norepinephrine/pharmacology* ; Plant Extracts ; Rats ; Rehmannia/chemistry* ; Serotonin/metabolism* ; Serotonin Plasma Membrane Transport Proteins/pharmacology* ; Stress, Psychological/metabolism* ; Tandem Mass Spectrometry ; Tryptophan Hydroxylase/metabolism*

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.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Cell Death* ; Dihydroxyphenylalanine ; Dopamine ; Dopaminergic Neurons* ; Homovanillic Acid ; Levodopa* ; Models, Animal* ; Norepinephrine ; Oxidopamine ; Parkinson Disease* ; Rats* ; Substantia Nigra ; Tyrosine 3-Monooxygenase

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.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; 3,4-Dihydroxyphenylacetic Acid ; Animals ; Carrier Proteins ; Dopamine ; Dopaminergic Neurons ; Homovanillic Acid ; Humans ; Learning ; Memory Disorders* ; Memory* ; Mice* ; N-Methylaspartate ; Norepinephrine ; Parkinson Disease* ; Phosphorylation ; Phosphotransferases ; Spatial Memory

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.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; 3,4-Dihydroxyphenylacetic Acid ; metabolism ; Acrylamides ; pharmacology ; Animals ; Caffeic Acids ; pharmacology ; Corpus Striatum ; metabolism ; Dopamine ; metabolism ; Homovanillic Acid ; metabolism ; Lipopolysaccharides ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity ; drug effects ; Neurons ; drug effects ; metabolism ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; pathology ; physiopathology ; Random Allocation ; Tyrosine 3-Monooxygenase ; metabolism

OBJECTIVETo 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.

METHODOvariectomized 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.

RESULTRg1 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).

CONCLUSIONGinsenoside 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.

3,4-Dihydroxyphenylacetic Acid ; Animals ; Behavior, Animal ; drug effects ; Central Nervous System Agents ; pharmacology ; Corpus Striatum ; drug effects ; metabolism ; Disease Models, Animal ; Dopamine ; metabolism ; Female ; Ginsenosides ; pharmacology ; Homovanillic Acid ; metabolism ; In Vitro Techniques ; Ovariectomy ; Parkinson Disease ; drug therapy ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo 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.

METHODSGroups 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.

RESULTSThe 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.

CONCLUSIONThese 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.

3,4-Dihydroxyphenylacetic Acid ; blood ; Animals ; Biogenic Monoamines ; blood ; Dimethoate ; toxicity ; Dopamine ; blood ; Dose-Response Relationship, Drug ; Epinephrine ; blood ; Male ; Norepinephrine ; blood ; Rats ; Rats, Sprague-Dawley ; Serotonin ; blood

OBJECTIVETo study the effects of deltamethrin on tyrosine hydroxylase in nigrostriatum of male rats.

METHODSSprague-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.

RESULTSThe 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.

CONCLUSIONSThese 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.

3,4-Dihydroxyphenylacetic Acid ; metabolism ; Animals ; Corpus Striatum ; drug effects ; metabolism ; Dopamine ; metabolism ; Gene Expression Regulation, Enzymologic ; Hominidae ; Insecticides ; toxicity ; Levodopa ; metabolism ; Male ; Nitriles ; toxicity ; Pyrethrins ; toxicity ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; metabolism ; Tyrosine 3-Monooxygenase ; genetics ; metabolism

OBJECTIVETo 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).

METHODOpen-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.

RESULTIn 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).

CONCLUSIONGYC 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.

3,4-Dihydroxyphenylacetic Acid ; metabolism ; Animals ; Behavior, Animal ; drug effects ; Biogenic Monoamines ; metabolism ; Cerebral Cortex ; metabolism ; Curcuma ; chemistry ; Depression ; etiology ; metabolism ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Dryopteris ; chemistry ; Male ; Olfactory Bulb ; pathology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism

OBJECTIVETo 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.

METHODThe 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.

RESULTAfter 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.

CONCLUSIONTZ 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.

3,4-Dihydroxyphenylacetic Acid ; metabolism ; Acetylcholine ; metabolism ; Animals ; Catecholamines ; metabolism ; Corpus Striatum ; metabolism ; Dopamine ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Extracellular Space ; metabolism ; Gastrodia ; chemistry ; Male ; Microdialysis ; Mitochondrial Diseases ; chemically induced ; metabolism ; Norepinephrine ; metabolism ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Sodium Azide ; Uncaria ; chemistry

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.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Brain ; Cerebellum ; Cerebral Cortex ; Chromatography, High Pressure Liquid ; Diet ; Dopamine ; Hippocampus ; Hydroxyindoleacetic Acid ; Hypothalamus ; Immunoassay ; Immunoenzyme Techniques ; Locus Coeruleus ; Metabolism ; Raphe Nuclei ; Rats* ; Receptors, Dopamine D2 ; Rhombencephalon ; RNA, Messenger ; Serotonin ; Substantia Nigra ; Synaptic Transmission* ; Ventral Tegmental Area