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Biomedical subjects

N Uchimura

Publications and source records attributed to N Uchimura.

At least 19 recordsLinked to original sources
PubMed1994

[Effects of mianserin hydrochloride on delirium: comparison with the effects of oxypertine and haloperidol].

Mianserin (10-60 mg), haloperidol (2-6 mg) and oxypertine (20-60 mg) were administered once before bedtime in patients with delirium in Kurume University Hospital. The therapeutic effects of these drugs were investigated in the pre- and post-treatment using Delirium Rating Scale (DRS: Trzepacz et al., 1988). Mianserin was observed to be effective on 67% of the cases, and haloperidol and oxypertine in about 60%. Based on the clinical results and on the measurement of plasma concentration of mianserin, mianserin was considered to be an effective drug particularly against delirium in elderly patients because the effect and plasma concentration of mianserin were observed in the early stage of treatment without any side effects. The reduction of plasma free-MHPG was accompanied with improvement in the delirious state. The reason for the changes in plasma free-HVA was unclear.

Adult↗
PubMed1993

Effects of zopiclone on slow wave sleep and spontaneous K-complexes for normal healthy young adults.

Benzodiazepine (BZD) hypnotics have been known to decrease, to some degree, human slow wave sleep (SWS) although they elevate the arousal threshold during sleep. Zopiclone (ZPC), a cyclopyrrolone hypnotic, has attracted the interest of sleep researchers because an increase in human SWS has been reported. Since the increase has not been fully confirmed by all of the studies, the authors investigated the effects of ZPC 10 mg on SWS and the K-complexes for 7 healthy young adults because there is evidence indicating that delta waves consisting of SWS and the spontaneous K-complexes are identical. SWS and st. 4 sleep did not decrease on any of the ZPC nights but st. 3 sleep showed a tendency to reduce on the 1st ZPC night. The frequency of the K-complexes decreased significantly on the 2nd ZPC night and tended to reduce on the 1st ZPC night. Moreover, a significant positive correlation was noted between the decrease rates of SWS and the K-complexes on both the ZPC nights. The authors, therefore, could not obtain any findings suggesting an increase in SWS with ZPC.

Administration, Oral↗
PubMed1992

A case of tardive Tourette-like syndrome.

We have had experience in treating tardive Tourette-like syndrome on a chronic schizophrenic patient. The patient was a 38-year-old woman. A diagnosis of schizophrenia was made in 1971 and she received repeated medications for 17 years. In 1989, she began to show vocal tic with coprolalia and motor tic. The medications were haloperidol 18 mg, zotepine 200 mg, levomepromazine 100 mg, biperiden 3 mg and nitrazepam 10 mg at the beginning of Tourette-like syndrome. We have tried to change the medications but this tardive Tourette-like syndrome continued to hang on. However, the symptoms gradually improved after a change in drugs; cessation of biperiden 3 mg and the administration of clonazepam 3 mg. The present case suggested that tardive Tourette-like syndrome might be a subtype of neuroleptic-associated tardive syndromes which might be treated with clonazepam.

Adult↗
PubMed1991

Distinct muscarinic receptors inhibit release of gamma-aminobutyric acid and excitatory amino acids in mammalian brain.

Intracellular recordings were made from neurons of rat lateral amygdala, nucleus accumbens, and striatum in vitro. Synaptic potentials mediated by gamma-aminobutyric acid and by excitatory amino acids were isolated pharmacologically by using receptor antagonists, and their amplitudes were used as a measure of transmitter release. Muscarine and acetylcholine inhibited the release of both gamma-aminobutyric acid and excitatory amino acids, but measurements of the dissociation equilibrium constants for the antagonists pirenzepine, 11-(2-[(diethylamino)methyl]-1-piperidinyl)acetyl-5,11-dihydro-6H-pyrido [2,3-b][1,4]benzodiazepine-6-one, methoctramine, and hexahydrosiladifenidol indicated clearly that different muscarinic receptors were involved (M1 and probably M3, respectively). The differential localization of distinct muscarinic receptor subtypes on terminals releasing the major inhibitory and excitatory transmitters of the brain could be exploited therapeutically in some movement disorders and Alzheimer disease.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Baclofen and adenosine inhibit synaptic potentials mediated by gamma-aminobutyric acid and glutamate release in rat nucleus accumbens.

Intracellular recordings were made from rat nucleus accumbens neurons in a tissue slice in vitro; postsynaptic potentials (p.s.p.) were evoked by focal electrical stimulation of the slice surface. P.s.p. were partially blocked by bicuculline (30 microM), partially blocked by a combination of 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX, 10 microM) and DL-2-amino-5-phosphonovaleric acid (APV, 30 microM) and completely blocked when all three antagonists were applied together. Both the gamma-aminobutyric acid (GABA)-mediated p.s.p. (in CNQX and APV) and the glutamate-mediated p.s.p. (in bicuculline) were inhibited by baclofen (10-300 microM), adenosine (10-300 microM) and N6-(2-phenylisopropyl)adenosine (0.1-3 microM). Theophylline competitively antagonized the action of adenosine with an apparent dissociation equilibrium constant of about 15 microM. Baclofen, adenosine and N6-(2-phenylisopropyl)adenosine caused small (less than 10 mV) hyperpolarizations; voltage clamp experiments indicated that this resulted from an outward potassium current. It is concluded that activation of GABAB receptors and adenosine A1 receptors inhibits the release of glutamate and GABA at synapses in the nucleus accumbens.

2-Amino-5-phosphonovalerate↗
PubMed1990

Actions of cocaine on rat nucleus accumbens neurones in vitro.

1. Intracellular recordings were made from 103 neurones of the rat nucleus accumbens in vitro. 2. Dopamine (3-100 microM; in sulpiride, 1 microM) hyperpolarized neurones (79%) by acting at D1 receptors: dopamine (3-100 microM; in SCH23390, 1 microM) depolarized neurones (55%) by acting at D2 receptors. 5-Hydroxytryptamine (1-100 microM) depolarized 86% neurones. 3. Both actions of dopamine as well as the effect of 5-hydroxytryptamine were potentiated by cocaine (0.3-30 microM), which had no effect of its own on membrane potential. 4. Dose-ratio was computed as [(concentration of agonist causing a 4 mV potential change in cocaine)/(concentration of agonist causing a 4 mV potential change without cocaine)]. Cocaine (1-30 microM) caused the same dose-ratio whether dopamine depolarizations (D2) or hyperpolarizations (D1) were measured; the dose-ratio ranged from 2 (1 microM) to 50 (30 microM). 5. Responses to 5-hydroxytryptamine were increased more than responses to dopamine; cocaine 1 microM gave a dose-ratio of 13.4 and at 30 microM gave a dose-ratio of 118. 6. It is concluded that cocaine acts to inhibit the uptake of dopamine and 5-hydroxytryptamine in slices of rat nucleus accumbens; lower concentrations of cocaine (0.3 to 1 microM) are particularly effective in potentiating the action of 5-hydroxytryptamine.

Animals↗
PubMed1990

Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones.

1. Intracellular recordings were made from neurones in the nucleus accumbens in slices from the rat brain maintained in vitro. 2. Muscarine (1-100 microM) depolarized 101 of 107 neurones; this was associated with an increase in the input resistance. The potential change reversed polarity with conditioning hyperpolarization and the reversal potential was linearly related to the logarithm of the extracellular potassium concentration. 3. The depolarization caused by muscarine was not changed by tetrodotoxin (1 microM) or by a solution that contained lower levels of calcium (0.24 instead of 2.4 mM), higher levels of magnesium (5 instead of 1.2 mM) and cobalt (2 mM). 4. Muscarine caused an inward current and a decrease in slope conductance when applied to neurones voltage clamped near their resting potential (-82 mV). The current caused by muscarine reversed polarity at the potassium equilibrium potential. The current-voltage relation of the neurones between -60 and -120 mV was well fitted by assuming a voltage-independent potassium conductance and an inward rectifier potassium conductance; muscarine reduced predominantly the inward rectifier conductance. 5. Phorbol-12,13-diacetate (3 microM) and 5-hydroxytryptamine mimicked the action of muscarine. The inward currents caused by muscarine or 5-hydroxytryptamine were occluded by the inward current evoked by the phorbol ester. 6. The depolarization caused by muscarine was competitively antagonized by pirenzepine; the dissociation constant of 11 nM suggested involvement of the M1 receptor. 7. It is concluded that muscarine acts at M1 receptors to reduce the membrane potassium conductance and that activation of protein kinase C may be an intermediate step.

Action Potentials↗
PubMed1990

Cation current activated by hyperpolarization in a subset of rat nucleus accumbens neurons.

1. Intracellular recordings were made from neurons in slices of rat nucleus accumbens in vitro. Membrane currents were measured in the potential range -60 to -120 mV with the use of a single-electrode, voltage-clamp amplifier. 2. A minority of neurons (28/285) was identified that had resting membrane potentials almost 20 mV less negative than the majority of the cells. These cells, but not the majority, had an inward current that activated slowly when the cells were hyperpolarized from -60 to -120 mV. The time constant of activation was approximately 3 s at -70 mV and 100 ms at -120 mV. 3. This inward current was completely blocked by external cesium (2 mM) but unaffected by barium. The current was reduced in solutions containing low-sodium concentration and increased in solutions with high-potassium concentration; its reversal potential was estimated to be -36 mV. 4. It is concluded that two types of neuron can be distinguished in the rat nucleus accumbens on the basis of the presence or absence of a cation current activated by hyperpolarization. This current (IH, also called If and IQ) causes the neurons to have less-polarized resting potentials than the majority of nucleus accumbens neurons.

Animals↗
PubMed1989

Enhancement of dopamine actions on rat nucleus accumbens neurones in vitro after methamphetamine pre-treatment.

1. Intracellular recordings were made from the nucleus accumbens neurons in brain slices from rats previously treated with saline or methamphetamine. 2. In neurones from both methamphetamine- and saline (control)-treated rats, dopamine (0.1 mM) produced three types of responses: a biphasic response consisting of an initial hyperpolarization followed by a depolarization, a monophasic hyperpolarization and a simple depolarization. 3. Haloperidol (1 microM) reversibly suppressed both responses to dopamine; (-)-sulpiride (1 microM) selectively abolished the depolarization and prolonged the hyperpolarization. Forskolin (10 microM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM) mimicked the hyperpolarization. Both of the latter two substances were more effective in neurones from methamphetamine-treated rats than in neurones from control rats. 4. In slices from methamphetamine-treated rats, the dose-response curve for the dopamine hyperpolarization was shifted to the left of that seen in neurones from control rats by a factor of approximately 100. The dose-response curve for the dopamine depolarization was shifted to the right about 10-fold in neurones from rats treated with methamphetamine. 5. In slices from control rats, dopamine (less than or equal to 0.1 mM) and methamphetamine (less than or equal to 1 microM) had no effect on the EPSPs evoked by focal electrical stimulation of the periaccumbens regions: dopamine (greater than or equal to 10 nM) and methamphetamine (1 microM) markedly depressed the EPSPs in slices from methamphetamine-treated rats. Depolarizations evoked by application of exogenous glutamate were unaffected by dopamine (less than 5 microM). 6. In slices from methamphetamine-treated rats, dopamine (greater than or equal to 10 nM), forskolin (greater than or equal to 1 microM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM) depressed Ca2+-dependent spikes as well as the EPSPs. Haloperidol (1 microM) completely reversed the depressions of the EPSPs and Ca2+-dependent spikes by dopamine, while (-)-sulpiride (1 microM) was only partially effective. 7. These results indicate that chronic methamphetamine administration leads to enhancement of the actions of dopamine at D1 receptors located on glutamate and/or aspartate nerve terminals and of the dopamine hyperpolarization of principal neurones, which is also mediated by D1 receptors.

Action Potentials↗
PubMed1989

5-Hydroxytryptamine acts at 5-HT2 receptors to decrease potassium conductance in rat nucleus accumbens neurones.

1. Intracellular recordings were made from neurones in the nucleus accumbens in slices from the rat brain maintained in vitro. 2. 5-Hydroxytryptamine (5-HT.1-100 microM) depolarized 170 of 203 (84%) neurones and caused them to discharge action potentials. The depolarization was associated with an increase in the input resistance, and was reversed in polarity by conditioning hyperpolarization; this reversal potential was linearly related to the logarithm of the extracellular potassium concentration. 3. Application of 5-HT to neurones voltage-clamped near their resting potential (typically about -80 mV) caused an inward current and a decrease in the slope conductance. The current caused by 5-HT reversed polarity at the potassium equilibrium potential. Analysis with an equivalent circuit model of the neurone at steady state indicated that 5-HT selectively reduced the inward rectifier potassium conductance. 4. The depolarization caused by 5-HT persisted in tetrodotoxin (1 microM). It was reduced but not abolished by a solution that contained lower levels of calcium (0.24 instead of 2.4 mM), higher levels of magnesium (5 instead of 1.2 mM), and cobalt (2 mM). 5. The depolarization caused by 5-HT was competitively antagonized by the 5-HT2 antagonists ketanserin and mianserin with dissociation equilibrium constants of 3 and 45 nM respectively: spiperone (300 nM) also blocked the action of 5-HT. The depolarization was not mimicked or blocked by a number of other agonists and antagonists selective for the 5-HT1 and 5-HT3 receptor types.

Animals↗
PubMed1989

Membrane properties and synaptic responses of the guinea pig nucleus accumbens neurons in vitro.

1. The membrane properties and synaptic responses of guinea pig nucleus accumbens neurons in vitro were studied with intracellular recording methods. 2. The population of neurons could be divided into groups of low (20-60 M omega, average 46.5 M omega) and high (60-180 M omega, average 96.5 M omega) input resistance. The resting membrane potential in both groups was approximately -70 mV. 3. Other membrane properties were quite similar in both groups. Inward rectification occurred at potentials more negative than -80 mV; this was blocked by Cs+ (2 mM). Membrane potential oscillations were observed at potentials between -65 and -55 mV; these were blocked by tetrodotoxin (TTX, 0.5 microM). Outward rectification occurred at potentials less negative than -45 mV; this was depressed by tetraethylammonium (TEA, 10 mM). 4. Action potentials elicited by small depolarizing current pulses (2-5 ms, 0.3-0.5 nA) were approximately 95 mV in amplitude and 1.0 ms in duration. The afterhyperpolarization following each action potential was less than 30 ms in duration, and no accommodation of action-potential discharge was seen at frequencies up to 40 Hz. The action potentials were reversibly blocked by TTX (0.3 microM). In addition, TTX-insensitive, Ca2+-dependent spikes were evoked by passing larger and more prolonged current pulses (greater than 40 ms, greater than 0.5 nA) across the membrane. 5. Focal electrical stimulation of the slice surface with low intensity (1 ms, less than 10 V) elicited excitatory postsynaptic potentials (EPSPs) in neurons of both high- and low-resistance groups. The reversal potential (+10.2 mV) for the EPSPs was close to the reversal potential (+7.7 mV) of the responses to glutamate applied in the superfusing solution. The N-methyl-D-aspartic acid (NMDA) receptor antagonists, D-alpha-aminoadipic acid (1 mM) and DL-2-amino-5-phosphonovaleric acid (DL-APV, 250 microM), reversibly depressed the EPSP; the glutamate uptake inhibitor, L-aspartic acid-beta-hydroxamate (50 microM), or removal of Mg2+ from the superfusate, augmented the EPSP. 6. When the intensity of the focal stimulus was increased (1 ms, greater than or equal to 10 V), a second larger depolarizing response (duration, 800 ms to 2 s) could be evoked in addition to the smoothly graded EPSP. This was seen only in cells of the high-resistance group (90-130 M omega).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

Inward rectification in rat nucleus accumbens neurons.

1. Intracellular recordings were made from neurons in slices cut from the rat nucleus accumbens septi. Membrane currents were measured with a single-electrode voltage-clamp amplifier in the potential range -50 to -140 mV. 2. In control conditions (2.5 mM potassium), the resting membrane potential of the neurons was -83.4 +/- 1.1 (SE) mV (n = 157). Steady state membrane conductance was voltage dependent, being 34.8 +/- 1.7 nS (n = 25) at -100 mV and 8.0 +/- 0.7 nS (n = 25) at -60 mV. 3. Barium (1 microM) markedly reduced the inward rectification and caused a small inward current (40.6 +/- 8.7 pA, n = 8) at the resting potential. These effects became larger with higher barium concentrations, and, in 100 microM barium, the current-voltage relation was straight. 4. The block of the inward current by barium (at -130 mV) occurred with an exponential time course; the time constant was approximately 1 s at 1 microM barium and less than 90 ms with 100 microM. Strontium had effects similar to those of barium, but 1000-fold higher concentrations were required. Cesium chloride (2 mM) and rubidium chloride (2 mM) also blocked the inward rectification; their action reached steady state within 50 ms. 5. It is concluded that the nucleus accumbens neurons have a potassium conductance with many features of a typical inward rectifier and that this contributes to the potassium conductance at the resting potential.

Animals↗
PubMed1988

Abnormal molecules of mitochondrial aspartate aminotransferase in the liver of vitamin B-6--deficient rats may be produced in the mitochondrial matrix.

The distribution of mitochondrial aspartate aminotransferase (AspATm) in liver cells was studied in rats fed pyridoxine-deficient and control diets. Mitochondrial aminotransferase activity was found mainly in the matrix fraction, with smaller amounts in the outer membranes, intermembrane space and cytosol. The precursor of the enzyme was detected in the liver cytosol of both vitamin B-6--deficient and control rats, and its amount was similar in the two groups. When pyridoxal phosphate was added to the assay system, the ratio of enzyme activity to antigenic activity (E/A) of mitochondrial aspartate aminotransferase in the cytosol of both vitamin B-6--deficient and control rats was about 70% of that in the matrix of control rats. On the other hand, the E/A of the matrix enzyme in deficient rats was 53% of that of controls. From these results we concluded that pyridoxal phosphate is not necessary for translocation of mitochondrial aspartate aminotransferase into mitochondrial matrix and that abnormal molecules of the enzyme may be formed in the matrix of vitamin B-6--deficient rat liver.

Animals↗
PubMed1986

Hyperpolarizing and depolarizing actions of dopamine via D-1 and D-2 receptors on nucleus accumbens neurons.

The effect of dopamine (DA) on the nucleus accumbens neurons in guinea-pig brain slices was studied by intracellular recordings. DA caused a hyperpolarization in 28% of the neurons tested, a depolarization in 11%, and a hyperpolarization followed by a depolarization in 53%. The remaining neurons were unaffected. Analyses of the responses revealed that the DA hyperpolarization was produced by activation of the D-1 receptor and associated with an increase in potassium conductance, whereas the DA depolarization was generated by activation of the D-2 receptor and accompanied by a decrease in potassium conductance. DA uptake inhibitors augmented both the hyperpolarizing and depolarizing responses, while cyclic adenosine monophosphate selectively enhanced the former.

Animals↗