ABSTRACT
RATIONALE: The present study hypothesized that delayed increases in extracellular glutamate (Glu) levels in the nucleus accumbens (NAC), induced by a high dose of methamphetamine (METH), can result in some functional changes of excitatory amino acid receptors, developing behavioral cross-sensitization to a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801. OBJECTIVES: The present study aims to examine whether two different doses of METH (2.5 and 1.0 mg/kg) induce different effects on the development of cross-sensitization to MK-801. To clarify the mechanisms for development and expression of cross-sensitization to MK-801, we measured extracellular Glu and dopamine (DA) levels in the NAC at METH injections in a treatment period and at MK-801 injection after a 12-day withdrawal period. MATERIALS AND METHODS: METH- or MK-801-induced changes in Glu and DA levels and in locomotion were measured using in vivo microdialysis and infrared sensor, respectively. RESULTS: METH, at only 2.5 mg/kg, produced delayed increases in Glu levels and developed behavioral cross-sensitization to MK-801 (0.2 mg/kg). MK-801 (0.2 mg/kg) induced delayed increases in Glu levels in the NAC, but this time course was not completely consistent with MK-801-induced enhanced hyperlocomotion. During this time course, MK-801 (0.2 mg/kg) did not induce any changes in DA levels. CONCLUSIONS: These results suggest that METH-induced, at 2.5 mg/kg, delayed increases in Glu levels are necessary for development of behavioral cross-sensitization to MK-801, but not METH. The enhanced locomotion-inducing effect of MK-801 might be related to some functional changes in excitatory amino acid receptors such as NMDA and DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid in the NAC.
Subject(s)
Dizocilpine Maleate/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Glutamic Acid/analysis , Methamphetamine/pharmacology , Nucleus Accumbens/drug effects , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Animals , Benzazepines/pharmacology , Dopamine/analysis , Dose-Response Relationship, Drug , Male , Microdialysis , Motor Activity/drug effects , Nucleus Accumbens/chemistry , Rats , Rats, Sprague-DawleyABSTRACT
RATIONALE: Our group has recently shown that methamphetamine (METH) (2.5 mg/kg) induced delayed increases in glutamate (Glu) levels in the rat nucleus accumbens (NAC), and that its repeated administration leads to behavioral cross-sensitization to a selective uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801). OBJECTIVES: The present study aims to examine whether valproate (VPA) would inhibit the delayed increases in Glu levels and prevent METH (2.5 mg/kg)-induced behavioral cross-sensitization to MK-801 (0.2 mg/kg). MATERIALS AND METHODS: We examined the effects of post-treated VPA (50 mg/kg) on METH (2.5 mg/kg)-induced delayed increases in Glu levels. We injected VPA (50 mg/kg) at 120 min after each METH (2.5 mg/kg, once every other day, total of five times) administration and measured locomotor activity induced by challenge with MK-801 (0.2 mg/kg) or METH (0.15 mg/kg) after sufficient withdrawal period. Finally, we measured locomotion induced by MK-801 (0.2 mg/kg) after pretreatment of a competitive NMDA receptor antagonist, CPP (30 mg/kg). Effects of VPA on extracellular Glu levels were examined by using in vivo microdialysis. Locomotor activity was measured by using an infrared sensor. RESULTS: VPA administered 120 min after METH injection had no effect on METH-induced hyperlocomotion, and inhibited METH-induced delayed increases in Glu levels. Repeated VPA administration prevented METH-induced behavioral cross-sensitization to MK-801, but not sensitization to METH. MK-801-induced hyperlocomotion was enhanced when pretreated with the competitive NMDA receptor antagonist, CPP. CONCLUSIONS: These results suggest that VPA inhibits high-dose METH-induced delayed increases in Glu levels to prevent development of behavioral cross-sensitization to an NMDA antagonist, but not sensitization to METH.
Subject(s)
Anticonvulsants/pharmacology , Behavior, Animal/drug effects , Central Nervous System Stimulants/pharmacology , Dizocilpine Maleate/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Locomotion/drug effects , Methamphetamine/pharmacology , Valproic Acid/pharmacology , Animals , Dose-Response Relationship, Drug , Drug Interactions , Glutamic Acid/metabolism , Male , Microdialysis , Neuronal Plasticity/drug effects , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/metabolism , Time FactorsABSTRACT
RATIONALE: In our preliminary study, methamphetamine (METH) at 2.5 mg/kg, but not at 1.0 mg/kg, induced a delayed increase in glutamate levels in the nucleus accumbens (NAc). We hypothesize that repeated increases in glutamate levels produces behavioral sensitization to a selective uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801), and that an activation of protein kinase C (PKC) plays an important role for this sensitization. OBJECTIVES: This study was conducted to confirm delayed increases in glutamate levels induced by a higher dose of METH (2.5 mg/kg), and to examine the effect of straurosporine, a PKC inhibitor, on the higher dose of METH-induced sensitization to dizocilpine. METHODS: The effects of METH on extracellular glutamate levels in the NAc were studied using in vivo microdialysis. Locomotor activity was measured by using an infrared sensor. RESULTS: METH at 2.5 mg/kg, but not at 1.0 mg/kg, induced delayed increases in glutamate levels. The acute administration of staurosporine did not affect the locomotor activity by a single injection of METH (2.5 mg/kg). Repeated METH administrations (2.5 mg/kg, once in every other day, for five times) developed behavioral sensitization to the locomotion-inducing effect of dizocilpine (0.2 mg/kg), a selective uncompetitive NMDA receptor antagonist. Staurosporine (0.1 mg/kg), given 120 min later for every METH treatment, inhibited the development of behavioral sensitization to dizocilpine. CONCLUSIONS: These results suggest the involvement of increased glutamate levels and an activation of PKC in delayed-induced synaptic and cellular plasticity underlying the higher dose of METH-induced behavioral sensitization to dizocilpine.
Subject(s)
Central Nervous System Stimulants/pharmacology , Dizocilpine Maleate/pharmacology , Enzyme Inhibitors/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Methamphetamine/pharmacology , Protein Kinase C/antagonists & inhibitors , Staurosporine/pharmacology , Animals , Behavior, Animal/drug effects , Dose-Response Relationship, Drug , Enzyme Inhibitors/administration & dosage , Glutamic Acid/biosynthesis , Male , Methamphetamine/administration & dosage , Motor Activity/drug effects , Rats , Rats, Sprague-Dawley , Staurosporine/administration & dosageABSTRACT
Single photon emission computed tomography was used to study 14 female patients with anorexia nervosa and 8 female normal comparison subjects. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Statistics across the entire brain were displayed as Z scores (threshold: P<0.05). Compared with the normal comparison subjects, the anorectic patients were characterized by hypoperfusion in the medial prefrontal cortex and the anterior cingulate gyrus, and hyperperfusion in the thalamus and the amygdala-hippocampus complex. These results suggest that a dysfunction in neuronal circuitry may be related to anorexia nervosa.
Subject(s)
Anorexia Nervosa/diagnostic imaging , Anorexia Nervosa/pathology , Brain Mapping/methods , Brain/blood supply , Cerebrovascular Circulation , Nerve Net/physiopathology , Tomography, Emission-Computed, Single-Photon , Adolescent , Adult , Anorexia Nervosa/physiopathology , Brain/diagnostic imaging , Case-Control Studies , Female , Frontal Lobe/blood supply , Humans , Iodine Radioisotopes , Radiopharmaceuticals , Technetium Tc 99m Exametazime , Temporal Lobe/blood supply , Thalamus/blood supply , Tomography, Emission-Computed, Single-Photon/methodsABSTRACT
The effects of lunchtime bright light exposure in patients of a geriatric hospital were investigated. Ten inpatients (six women and four men; mean age +/- SD: 81.2 +/- 8.8 years) with sleep disturbances were studied for 9 weeks. Nurses performed daily ratings for sleep-wakefulness disturbances. Approximately 8000 lx bright light exposure was performed for 3 weeks in the light therapy room. Before and after exposure, ocular function was evaluated. Clinical ratings of sleep-wakefulness improved in eight patients. The score of difficulty in falling asleep and drowsiness in the morning declined during the light exposure. The score of drowsiness in the afternoon decreased during the post-light exposure. Post-exposure ocular disturbances were not found.
Subject(s)
Eating , Health Services for the Aged , Light , Sleep Disorders, Circadian Rhythm/therapy , Sleep/physiology , Aged , Aged, 80 and over , Female , Hospitals , Humans , Male , Phototherapy/methodsABSTRACT
Inpatients with sleep disturbances in a geriatric hospital received 1 h of exposure to approximately 8000 lx bright light per day for 3 weeks. Polysomnogram was recorded for four female patients. Two (aged 68 and 87 years) were non-demented patients with weak cataracts and the other two (aged 92 and 93 years) were demented patients with severe cataracts. Electroencephalogram results showed that light exposure decreased the proportion of Stage W, while increased the proportion of Stage 2, and these effects continued for at least 3 weeks after the cessation of light exposure. These results suggest that exposure to bright light is effective in improving the disturbed sleep of patients.
Subject(s)
Eating , Health Services for the Aged , Hospitals , Light , Aged , Aged, 80 and over , Electroencephalography , Female , Humans , Phototherapy/methods , Polysomnography , Sleep Disorders, Circadian Rhythm/therapy , Sleep Stages/physiologyABSTRACT
OBJECTIVE: Sepsis is a major cause of adult respiratory distress syndrome. In this study, we evaluated the effect of FR167653, which is a potent suppressant of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 production, on lipopolysaccharide (LPS)-induced lung injury and lethality in rats, and we examined the involvement of p38 mitogen-activated protein (MAP) kinase in the action of FR167653. DESIGN: Prospective, randomized study. SETTING: Animal research facility in a university. SUBJECTS: Male Sprague-Dawley rats weighing 200-270 g. INTERVENTIONS: All the animals were assigned to one of the following four groups: control group, FR-only group, LPS-only group, and LPS/FR group. Animals in the LPS-only and LPS/FR groups received 6 mg/kg of LPS intravenously. The animals in the FR-only and LPS/FR groups also received an infusion of FR167653 at 0.2 mg x kg(-1) x hr(-1), commencing 30 mins before the LPS (or vehicle) injection and continuing for 5.5 hrs. MEASUREMENTS AND MAIN RESULTS: LPS significantly induced the accumulation of pulmonary neutrophils and lung edema, both of which were significantly attenuated by treatment with FR167653. FR167653 also significantly decreased the LPS-induced lethality. Histologically, tissue damage was milder in the LPS/FR group than in the LPS-only group. Serum concentrations of TNF-alpha and IL-1beta and plasma concentrations of thromboxane B2 were all suppressed in the LPS/FR group compared with the LPS-only group. Western blot analysis revealed that FR167653 inhibited the phosphorylation of p38 MAP kinase in lung tissues. CONCLUSIONS: FR167653 administration decreased serum TNF-alpha and IL-1beta concentrations, which was associated with decreased lung injury and lethality. The mechanism responsible for the decreased TNF-alpha and IL-1 may be related to the inhibitory effect of FR167653 on p38 MAP kinase activation.
Subject(s)
Disease Models, Animal , Escherichia coli Infections/complications , Escherichia coli , Immunosuppressive Agents/therapeutic use , Interleukin-1/antagonists & inhibitors , Lipopolysaccharides , Mitogen-Activated Protein Kinases/drug effects , Pyrazoles/therapeutic use , Pyridines/therapeutic use , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/microbiology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Drug Evaluation, Preclinical , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/immunology , Interleukin-1/blood , Interleukin-1/immunology , Lung/chemistry , Male , Mitogen-Activated Protein Kinases/analysis , Prospective Studies , Pyrazoles/chemistry , Pyrazoles/immunology , Pyridines/chemistry , Pyridines/immunology , Random Allocation , Rats , Rats, Sprague-Dawley , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/mortality , Survival Analysis , Thromboxane B2/blood , Time Factors , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein KinasesABSTRACT
BACKGROUND: Interictal brain single photon emission computed tomography (SPECT) is useful for the detection of seizure focus. Recent reports indicate a hypoperfusion in the ipsilateral thalamus as a seizure focus on interictal SPECT in temporal lobe epilepsy. In frontal lobe epilepsy (FLE), however, the alteration of perfusion in the thalamus has not been well documented. This study aimed to assess whether perfusion analysis on the thalamus may add useful information for the detection of epileptic foci in patients with FLE. METHODS: Interictal brain SPECT was performed in 11 patients with FLE. The asymmetry index for the thalamus and frontal area in the SPECT image was calculated in order to compare the laterality of the seizure foci. RESULTS: Thalamic asymmetry was seen in seven patients (64%), while cortial asymmetry was seen in six patients (55%). The concordance with the lateralization of the seizure foci was 6/7 (86%) in the thalamus, and 4/6 (67%) in the frontal area. Four patients showed only thalamic asymmetry. Concordance with the lateralization of the seizure focus was found in all of them. CONCLUSION: These preliminary results suggest that hypoperfusion in the thalamus may have a complementary role to lateralize the epileptic foci in patients with FLE.
Subject(s)
Epilepsy, Frontal Lobe/diagnostic imaging , Thalamus/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Adolescent , Adult , Amphetamines/pharmacokinetics , Electroencephalography , Epilepsy, Frontal Lobe/physiopathology , Epilepsy, Temporal Lobe/diagnostic imaging , Female , Functional Laterality , Humans , Iodine Radioisotopes/pharmacokinetics , Male , Middle Aged , Radiopharmaceuticals/pharmacokinetics , Reproducibility of Results , Thalamus/physiopathologyABSTRACT
The toxic dose of methamphetamine (METH) (5 mg/kg, s.c., x4, 2 hr intervals) decreased contents of dopamine, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in striatum, and decreased contents of serotonin (5-HT) in both striatum and nucleus accumbens. Administration of low doses of a non-selective endothelial and neuronal nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) (5 and 10 mg/kg, i.p., x1) intensified the METH-induced decreases in contents of dopamine and its metabolites in striatum. NO substrate, L-arginine (500 mg/kg, i.p., x4) reversed these effects of L-NAME on the METH-neurotoxicity. L-NAME did not change the METH-induced hyperthermia. These findings, which are contrary to our previous study with a high dose of L-NAME, suggest that the inhibition of endothelial or neuronal NOS-mediated NO production by low doses of L-NAME enhanced the METH-induced neurotoxicity. The finding that L-NAME can have opposite effects on the METH-neurotoxicity according to the dosing is important, however, additional experiments should be performed to clarify which type of NOS is related to these effects.
Subject(s)
Corpus Striatum/drug effects , Dopamine Uptake Inhibitors/pharmacology , Dopamine/metabolism , Methamphetamine/pharmacology , NG-Nitroarginine Methyl Ester/administration & dosage , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Body Temperature/drug effects , Body Temperature/physiology , Corpus Striatum/metabolism , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Synergism , Fever/chemically induced , Fever/metabolism , Injections, Subcutaneous , Male , Rats , Rats, Wistar , Serotonin/metabolismABSTRACT
This book is well preserved in the Ashimori Kaikan (an exhibit of Okayama city). This paper describes the book of medicinal plants in detail.
Subject(s)
Books/history , Medical Illustration/history , Plants, Medicinal , Exhibitions as Topic , History, 20th Century , History, Modern 1601- , JapanABSTRACT
In order to investigate the effects of 5000 lx evening bright light on autonomic nervous function, a spectral analysis was used to assess heart rate variability in consecutive 5-min epochs just after 60 min of bright light therapy was given to 12 young women (range: 20-21 years of age). The study revealed that a low frequency band (LF) increased in bright light conditions (BL) in comparison with controlled conditions (CL). High frequency band (HF), LF:HF ratio and the coefficient of variance (CV R-R) were not significantly different between the two conditions. These results indicate that 5000 lx evening bright light may affect sympathetic nervous system activity in healthy women.
Subject(s)
Autonomic Nervous System/physiology , Circadian Rhythm/physiology , Heart Rate/physiology , Phototherapy , Adult , Arousal/physiology , Electrocardiography , Female , Fourier Analysis , Humans , Signal Processing, Computer-Assisted , Sympathetic Nervous System/physiologyABSTRACT
To investigate the effects of 8000 lux morning bright light in the elderly, home-based motor activity on sleep was monitored for 5 days in 10 healthy women (mean age: 59.7 years old, range: 50-69 years old). The activity level and movement index on night 4 were significantly lower in bright light conditions, compared with the controlled condition. The activity level during the day was not significantly different between the two conditions. These results indicate that 8000 lux morning bright light improves sleep quality in healthy elderly women.
Subject(s)
Aging/psychology , Circadian Rhythm , Motor Activity , Phototherapy , Aged , Arousal , Female , Humans , Middle Aged , Sleep Stages , WakefulnessABSTRACT
Subjective sleep feeling and polysomnography were measured in 10 elderly women to investigate the effects of 8000 lux morning bright light (BL) exposure. The profile of sleep feeling in the BL condition was better than in the control condition. The proportion of awakening time in the first one-third of night sleep decreased, and the amount of awakening time in the last one-third increased in BL condition. Daytime napping reduced in BL condition. These findings suggested the effectiveness of exposure to bright light on the improvement of sleep quality and daytime vigilance of healthy elderly women.
Subject(s)
Aging/psychology , Circadian Rhythm , Phototherapy , Sleep Stages , Aged , Arousal , Female , Humans , Middle Aged , Polysomnography , Treatment Outcome , WakefulnessABSTRACT
Four patients were treated by placement of an expandable metallic stent (two Gianturco Z-stents, two Ultraflex stents) for malignant colorectal strictures. All four patients were able to defecate after stent placement. Stent migration was recognized in one patient. Two patients suffered from tenesmus after stent placement.
Subject(s)
Colorectal Neoplasms/complications , Rectum/pathology , Stents , Aged , Barium Sulfate , Colorectal Neoplasms/diagnostic imaging , Constriction, Pathologic/diagnostic imaging , Constriction, Pathologic/etiology , Constriction, Pathologic/therapy , Defecation , Enema , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Radiography , Rectum/diagnostic imaging , Treatment OutcomeABSTRACT
The effect of hepatic arterial infusion chemotherapy on the prognosis after hepatectomy for hepatocellular carcinoma was investigated in patients with risk factors for recurrence. The risk factors for recurrence after hepatectomy were defined to be metastasis in the liver (+), portal tumor embolus (+), and tumor larger than 5 cm in diameter. Out of 87 patients with hepatocellular carcinoma who underwent an operation in the past 7 years in our hospital, 60 survived for more than 1 year and were enrolled in our study. Thirty-eight of them showed one or more risk factors for recurrence, and were considered to be the high-risk group. These 38 patients were divided into two groups: one group of 19 treated by hepatic arterial infusion chemotherapy using mitoxantrone, and the other group of 19 given no treatment. The survival rates and non-recurrence rates were compared between the two groups. The survival rates after 1 and 3 years for the group treated by hepatic arterial infusion chemotherapy were 94.7% and 54.7%, respectively. The survival rates for the non-treated group were 53.9% and 32.8%, respectively (p = 0.012). The non-recurrence rates after 1 year and 3 years were 94.7% and 44.2% for the treated group and 52.6% and 23.6% for the non-treated group (p = 0.005), respectively. The survival rates and non-recurrence rates after 3 years in the treated group were significantly higher (p = 0.012, 0.005), respectively. It was concluded, therefore, that post-operation hepatic arterial infusion chemotherapy improved the prognosis of the high-recurrence probability group.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Hepatocellular/therapy , Hepatectomy , Liver Neoplasms/therapy , Mitoxantrone/administration & dosage , Antibiotics, Antineoplastic/administration & dosage , Carcinoma, Hepatocellular/surgery , Doxorubicin/administration & dosage , Embolization, Therapeutic , Female , Hepatic Artery , Humans , Infusions, Intra-Arterial , Iodized Oil/administration & dosage , Liver Neoplasms/surgery , Male , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
This article describes the clinical problems encountered with the use of hyperthermia equipment and the requisites in the development of more advanced systems. A summary of the trends in the development of hyperthermia equipment is presented. In addition, a description from the physical point of view is included for the design of new applicators for deep heating.
Subject(s)
Hyperthermia, Induced/instrumentation , Electrodes , Hot Temperature , Hyperthermia, Induced/trends , Magnetic Resonance Spectroscopy , Microwaves/therapeutic use , Neoplasms/therapy , Radiotherapy , Software , Temperature , Tomography, X-Ray Computed , UltrasonicsABSTRACT
We examined effects of nitric oxide (NO.) synthesis inhibition on methamphetamine (MA)-induced dopaminergic and serotonergic neurotoxicity. The toxic dose of MA (5 mg/kg, sc, x4) significantly decreased contents of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum (ST), and significantly decreased contents of serotonin (5-HT) in the ST, nucleus accumbens (NA) and medial frontal contex (MFC). Coadministration with a NO. synthase inhibitor, N omega-nitro-L-arginine methyl ester (LNAME) (30 mg/kg, i.p., x2), reduced the MA-induced decreases in contents of DA, DOPAC and HVA in the ST, but not reduced the MA-induced decreases in contents of 5-HT in the ST, NA and MFC. These findings suggest that the MA-induced dopaminergic, but not serotonergic neurotoxicity, may be related to the neural process such as NO. formation caused by the activation of postsynaptic DA receptor.
Subject(s)
Brain Chemistry/drug effects , Dopamine Uptake Inhibitors/pharmacology , Methamphetamine/pharmacology , Neurotoxins/pharmacology , Nitric Oxide/biosynthesis , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Biogenic Monoamines/metabolism , Dopamine/adverse effects , Dopamine/metabolism , Enzyme Inhibitors/pharmacology , Frontal Lobe/drug effects , Frontal Lobe/metabolism , Homovanillic Acid/metabolism , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/antagonists & inhibitors , Rats , Rats, Wistar , Serotonin/adverse effects , Serotonin/metabolism , Sodium Chloride/pharmacologySubject(s)
Bipolar Disorder/therapy , Circadian Rhythm , Phototherapy , Vitamin B 12/administration & dosage , Adult , Bipolar Disorder/physiopathology , Bipolar Disorder/psychology , Body Temperature Regulation/physiology , Circadian Rhythm/physiology , Combined Modality Therapy , Drug Administration Schedule , Humans , Male , Sleep Stages/physiologyABSTRACT
We examined effects of a high dose of methamphetamine (MA) (4.02 mg free base/kg, s.c., at 2-h intervals, 4 injections) on extracellular concentrations of monoamines such as dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) and those of glutamate and other several amino acids in rat striatum (ST) and nucleus accumbens (NA) using in vivo microdialysis. Five days after the microdialysis, tissue concentrations of monoamines were measured. The toxic dose of MA markedly increased extracellular concentrations of DA, and decreased those of DOPAC, HVA and 5-HIAA in both ST and NA. Magnitude of the increase in DA release was not different between ST and NA. Extracellular concentrations of glutamate showed a gradual increase in ST, but not in NA, while other amino acids showed no changes in both ST and NA. Tissue concentrations of serotonin (5-HT) and 5-HIAA were decreased to 43-58% of control values in both ST and NA, whereas those of DA, DOPAC and HVA showed 43-54% decrease in ST but no changes in NA. These data suggest that the marked increase of DA release is not directly related to the MA-induced dopaminergic neurotoxicity. The increase in glutamate release found only in ST may be related to the dopaminergic damage in ST. It may be that enhanced release in DA and glutamate act synergistically to cause the dopaminergic neurotoxicity in ST. However, enhancement in glutamate release did not appear to be essential for the MA-induced serotonergic neurotoxicity.