No abstract available.
3,4-Dihydroxyphenylacetic Acid* ; Animals ; Brain* ; Diazepam* ; Rats*

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(P<0.05). Dopamine mostly increased during hypoxia but statistically not significant(P>0.05). 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.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Anoxia ; Brain* ; Carotid Artery, Common ; Cerebrospinal Fluid ; Dopamine ; Humans ; Hydroxyindoleacetic Acid ; Infant, Newborn ; Metabolism* ; Microdialysis ; Rats*

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.
3,4-Dihydroxyphenylacetic Acid ; Antioxidants ; Brain ; Bromocriptine* ; Cell Line ; Dopamine ; Dopamine Agonists ; Humans ; Lipid Peroxidation* ; Neuroblastoma ; Oxidopamine ; Parkinson Disease

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.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Brain ; Chromatography, Liquid ; Clonidine ; Depression ; Hippocampus* ; Hydroxyindoleacetic Acid ; Idazoxan ; Metabolism ; Methoxyhydroxyphenylglycol ; Microdialysis ; Norepinephrine ; Rats* ; Serotonin ; Visual Cortex* ; Yohimbine

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

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.
3,4-Dihydroxyphenylacetic Acid ; Animals ; Brain* ; Chromatography, Liquid ; Dialysis Solutions ; Homovanillic Acid ; Hypothalamus ; Hypothalamus, Posterior* ; Imipramine ; Microdialysis* ; Monoamine Oxidase Inhibitors ; Neurons ; Neurotransmitter Agents ; Norepinephrine* ; Pargyline ; Potassium ; Rats*

Recently oxygen free radicals and nitric oxide (NO) are known to play an important role in neuronal reperfusion injury. This study was aimed to investigate the role of oxygen f ree radicals and NO during cerebral ischemia/reperfusion, using dimethylthiourea (DMTU) and NG-monomethyl-L-arginine (NMMA), an oxygen f ree radical scavenger and a competitive NOS inhibitor respectively. In the in vivo experiment, the ischemia/reperfusion-induced changes of cerebral biogenic amines were examined in Mongolian gerbil (Meriones unguiculatus) pre-treated with NMMA and/or DMTU. To induce cerebral ischemia/reperfusion, bilateral common carotid arteries were clamped for 10 minutes and then released for 15 minutes. The biogenic amines were measured by using HPLC-ECD(High Performance Liquid Chromatography-Electrochemical detection). To confirm the results from the in vivo experiments, the effect of NMMA and/or DMTU on [3H]dopamine release from striatal slices exposed to hypoxia was investigated. The results are as follows; 1) Ischemia/reperfusion increased the ratio of DOPAC/dopamine and HVA/dopamine as well as the concentrations of DOPAC and HVA, which were evident only in corpus striatum. 2) NMMA attenuated the ischemia/reperfusion-induced increase in the ratio of DOPAC/dopamine in corpus striatum. However, the change of DOPAC or HVA was minimal. 3) DMTU attenuated the ischemia/reperfusion-induced increase of DOPAC and HVA, and the ratio ofDOPAC / dopa- mine and HVA/dopamine in corpus striatum. 4) Simultaneous pre-treatment with NMMA and DMTU attenuated the ischemia/reperfusion-induced increase of DOPAC and HVA, and the ratio Of DOPAC/dopamine and HVA/dopamine in corpus striatum. The extent of attenuation was greater than the single treatment group with NMMA or DMTU. 5) Exposure to hypoxia markedly increased the release of [3H]dopamine in the striatal slices. 6) The administration of either NMMA or DMTU attenuated the increase of [3H]dopamine release induced by hypoxia in the striatal slices. 7) The administration of both NMMA or DMTU markedly attenuated the increase of [3H]dopamine release induced by hypoxia to the extent of the control in the striatal slices. These results suggest that oxygen free radicals play an important role in cerebral ischemia/reperfusion injury, for which NO seems to be responsible.
3,4-Dihydroxyphenylacetic Acid ; Anoxia ; Biogenic Amines* ; Carotid Artery, Common ; Corpus Striatum ; Dopamine ; Free Radicals* ; Gerbillinae ; Ischemia ; Neurons ; Nitric Oxide* ; omega-N-Methylarginine ; Oxygen* ; Reperfusion ; Reperfusion Injury

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.
3,4-Dihydroxyphenylacetic Acid ; Brain ; Diagnosis ; Dopamine ; Epinephrine ; Female ; Follicular Phase ; Galactorrhea ; Humans ; Hyperprolactinemia ; Infertility ; Lactotrophs ; Methoxyhydroxyphenylglycol ; Norepinephrine ; Pregnancy ; Prolactinoma ; Reference Values

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

After the ischemic episode. A new cerebral damage can occur during the restitution of blood flow. Oxygen free radicals. Formed during ischemia/reperfusion. Have been proposed as one of the main causes of reperfusion injury. Altered concentrations of brain biogenic arnines are also reported in ischemia or reperfusion. However, a paucitv in inforrnation and controversy, in the mechanism of the brain darnage during reperfusion still remain. In the present study. Therefore. The ischemia- and/or reperfusion-induced changes in biogenic amines were measured from rat brain regions.. Furthermore. The ability of free radical scavengers (Superoxide dismutase, catalase, allopurinol and deferoxamine) to prevent changes in brain biogenic amines was also investigated. To induce brain ischemia/reperfusion, bilateral common carotid arteries were clamped for 30 minutes and thereafter the.clamps were removed to reperfuse for 15 minutes. The concentrations of biogenic amines and their metabolites (dopamine- 3,4-dihydroxy phenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA)) in various brain regions, including frontal cortex, corpus striatum. Hippocampus and thalamus; were measured using the high performance liquid chromatography with electrochemical detector. The results are as follows: 1. In the ischemia group the concentrations of DOPAC and the ratio of DOPAC/dopamine were increased and the ratio of HVA/DOPAC was decreased. Which were evidently only in corpus striatum.
3,4-Dihydroxyphenylacetic Acid ; Allopurinol ; Animals ; Biogenic Amines* ; Brain* ; Carotid Artery, Common ; Catalase ; Chromatography, Liquid ; Corpus Striatum ; Free Radical Scavengers ; Free Radicals* ; Hippocampus ; Homovanillic Acid ; Ischemia ; Oxygen ; Rats* ; Reperfusion ; Reperfusion Injury ; Serotonin ; Thalamus