Biomedical subjects

K Emori

Publications and source records attributed to K Emori.

At least 19 recordsLinked to original sources

PubMed2001

Intracerebroventricular administration of NMDA-R1 antisense oligodeoxynucleotide significantly alters the activity of ventral tegmental area dopamine neurons: an electrophysiological study.

In this study, we determined the activity of midbrain dopamine (DA) neurons in male albino rats following the intracerebroventricular (i.c.v.) administration of antisense oligodeoxynucleotide (aODN) against the mRNA for the NR1 subunit of the NMDA receptor. In addition, the effect of aODN on the specific binding of the NMDA receptor ligand [(3)H]MK-801 was also examined in various brain areas, including the midbrain. Antisense ODN against the NR1 mRNA, the corresponding sense ODN (sODN) or saline was continuously administered into the right ventricle of rats by osmotic minipumps for 7 days (20 nmol/day). Autoradiographic binding studies indicated that aODN significantly reduced the density of [(3)H]MK-801 binding by an average of 20-30% in several forebrain regions, including the anterior cingulate cortex, caudate putamen, and nucleus accumbens. However, [(3)H]MK-801 binding was not significantly altered in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNC). Subsequently, using the technique of extracellular single-unit recording, the number, as well as the firing pattern, of spontaneously active DA neurons was determined in the VTA and SNC. The administration of aODN did not significantly alter the number of spontaneously active VTA and SNC DA neurons compared to saline- of sODN-treated animals. Furthermore, the firing pattern of spontaneously active SNC DA neurons was not significantly altered. However, for spontaneously active VTA DA neurons, the administration of aODN significantly decreased the percent events in bursts, number of bursts, and percentage of DA neurons exhibiting a bursting pattern compared to saline- and sODN-treated animals, i.e., neurons show less bursting activity. The present results suggest that subchronic aODN treatment against the mRNA for the NR1 subunit of the NMDA receptors can reduce NMDA receptor number and can result in an altered activity of spontaneously active VTA DA neurons in anesthetized rats.

Action Potentials↗

PubMed1997

Changes in paired-pulse depression during the triggering of seizures by 2 Hz dentate gyrus stimulation: effect of the kindling.

In this study, seizures in the dentate gyrus were triggered by 2 Hz electrical stimulation while, at the same time, serial changes in paired-pulse depression was measured in free-moving rats. The perforant path was stimulated by paired pulses 25 ms apart and recordings were made in the dentate gyrus. We also observed the effect of kindling procedure on this change of evoked field potential. Paired-pulse depression started to fail following the onset of epileptic afterdischarge, both before and after kindling. As kindling progressed, paired-pulse depression increased in the initial part of the stimulus train, and also the time delay from the start of the stimulation to when paired-pulse depression started to fail increased significantly. These findings suggest that the collapse of local early, presumably GABAA-mediated, inhibition may occur after the dentate gyrus seizure onset and development of kindling epileptogenesis does not weaken but, on the contrary, enhances this local inhibitory function. Finally we propose that seizures triggered by 2 Hz electrical stimulation constitutes a useful model for examining physiological or biochemical changes during seizure initiation of awake, free-moving animals since it provides long (usually several seconds or more) latency from the start of stimulation to seizure onset.

Animals↗

PubMed1996

The effect of the acute and chronic administration of CP 96,345, a selective neurokinin1 receptor antagonist, on midbrain dopamine neurons in the rat: a single unit, extracellular recording study.

In this study, we examined the effect of acute and chronic administration of the selective neurokinin1 receptor antagonist CP 96,345 on the basal activity of spontaneously active dopamine (DA) neurons in the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA). This was accomplished using the technique of in vivo, extracellular single unit recording in anesthetized rats. The intravenous (i.v.) administration of CP 96,345 (0.01-1.28 mg/kg) did not significantly alter the firing rate of spontaneously active DA neurons in the SNC and VTA areas. The acute administration of 5 or 10 mg/kg, i.p., of CP 96,345 produced a significant decrease in the number of spontaneously active SNC and VTA dopamine cells compared to vehicle-treated rats. In contrast to its effect on the number of spontaneously active DA neurons, the administration of 5 mg/kg, i.p., of CP 96,345 did not significantly alter the basal firing pattern of either SNC or VTA DA neurons. The acute administration of CP 96,345 (10 mg/kg, i.p.) significantly potentiated the suppressant action of (+)-apomorphine on the basal firing rate of spontaneously active SNC and VTA DA cells. The chronic administration of CP 96,345 (5 or 10 mg/kg, i.p.) for 21 days also produced a significant decrease in the number of spontaneously active SNC and VTA DA cells compared to vehicle controls. This effect was not reversed by the systemic administration of (+)-apomorphine (50 micrograms/kg, i.v.), suggesting that the reduction in the number of spontaneously active DA cells produced by CP 96,345 is probably not the result of depolarization inactivation. Overall, our results indicate that the tonic activation of NK1 receptors by substance P may be necessary to maintain the spontaneous activity of a proportion of midbrain DA neurons.

Animals↗

PubMed1996

The depletion of brain serotonin levels by para-chlorophenylalanine administration significantly alters the activity of midbrain dopamine cells in rats: an extracellular single cell recording study.

In this study, we examined the effect of 5-HT depletion produced by the acute administration of para-chlorophenylalanine (PCPA) on the number of spontaneously active dopamine (DA) cells in the ventral tegmental area (VTA or A10) and substantia nigra pars compacta (SNC or A9) in the rat. We also determined the effect of PCPA administration on the spike discharge pattern of midbrain DA cells. This was accomplished using standard extracellular single cell recording techniques. The administration of PCPA (400 mg/kg, i.p., 24 h before the experiment) produced a significant decrease in the number of spontaneously active DA cells in both the A9 (52%) and A10 (63%) areas compared to controls. The burst firing analysis indicated that there was a significant increase in the mean interspike interval of A9 and A10 DA neurons in PCPA treated animals compared to controls. Furthermore, a decrease in the percentage of A10 DA neurons exhibiting a burst firing pattern and the number of bursts was observed in the PCPA treated animals compared to controls. The intravenous (i.v.) administration of 5-hydroxytryptophan (40 mg/kg) and the peripheral aromatic acid decarboxylase inhibitor benserazide (10 mg/kg) which restores 5-HT content, reversed the decrease in the number of spontaneously active A9 and A10 DA neurons, as well as the decrease in the percentage of A10 DA neurons exhibiting a bursting pattern. In contrast, the i.v. administration of benserazide (10 mg/kg) and L-DOPA (40 mg/kg) did not reverse the decrease in the number of spontaneously active midbrain DA neurons produced by PCPA treatment. The pretreatment of animals with PCPA did not alter the sensitivity of spontaneously active A9 or A10 DA cells to the intravenous administration of (+)-apomorphine (1-32 micrograms/kg) compared to controls. Overall, our results indicate that the depletion of brain 5-HT by PCPA produces a decrease in the activity of midbrain DA cells, suggesting that endogenous 5-HT is required to maintain DA tone.

5-Hydroxytryptophan↗

PubMed1995

Significant differences in the activity of midbrain dopamine neurons between male Fischer 344 (F344) and Lewis rats: an in vivo electrophysiological study.

There is a significant difference between the Lewis and Fischer 344 rats regarding their propensity to self-administer drugs of abuse. This study compares the number and the firing pattern of spontaneously active dopamine (DA) neurons in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in these two strains of rats. This was accomplished using the technique of in vivo extracellular recording. The number of spontaneously active DA neurons in the SNC and VTA of the Lewis rat were significantly lower compared to that of the F344 rats. Furthermore, a greater percentage of SNC and VTA DA neurons in the Lewis rats exhibited a burst firing pattern compared to F344 rats. These findings indicate that F344 and Lewis rats possess differences in mesolimbic DA neuronal activity and this may be a factor in explaining the different propensities between the two strains to self-administer drugs.

Animals↗

PubMed1993

Effects of long-stimulus intervals and scopolamine administration on hippocampal kindling.

Using the low-frequency kindling procedure, we studied the effects of periodic 2-week stimulus-free intervals and chronic scopolamine administration on hippocampal kindling seizure development. In Experiment 1, rats were divided into two groups, interval group and no-interval group. In the interval group a 2-week stimulus interval was set after every five consecutive daily stimulations until the 21st stimulation. The number of stimulating pulses required for the triggering of epileptic afterdischarge, pulse-number threshold (PNT), was used as an indicator of the seizure threshold. PNT, afterdischarge duration (ADD) and behavioral seizure stage (BSS) of each induced seizure in the initial stage of kindling, kindling rate, seizure parameters at the completion of kindling were recorded and compared to the values of the no-interval, control group. Our result showed that PNT at the 6th stimulation, the first stimulation after the first 2-week stimulus interval increased significantly compared to control. Other seizure parameters did not differ significantly between the two groups. In Experiment 2 scopolamine hydrobromide, 0.5 and 1.0 mg/kg i.p., was administered 1 h before each electrical stimulation until each rat showed the stage-3 seizure. PNT, ADD and BSS in the initial stage of kindling, kindling rate for the stage-3 and -5 seizures, seizure parameters at the first stage-3 and -5 were recorded and compared to the values of saline-treated, control group. Although scopolamine 1.0 mg/kg increased PNT at the 5th stimulation compared to control, no other significant changes of the seizure parameters were found by scopolamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Two types of neuroplasticities in the kindling phenomenon: effects of chronic MK-801 and methamphetamine.

Using the low-frequency kindling technique, we studied the effects of chronic MK-801 and chronic methamphetamine (MAP) administration on hippocampal kindling seizure development. In experiment 1, MK-801 (0.05, 0.1 mg/kg i.p.) was administered 2 h before each electrical stimulation until kindling developed into stage-3 seizure. In experiment 2, we started daily electrical stimulations two weeks after the last injection of chronic MAP administration (6 mg/kg/day, 14 days). The number of stimulating pulses required for the triggering of epileptic afterdischarge (pulse-number threshold, PNT) was used as an indicator of the seizure threshold. PNT, afterdischarge duration (ADD) and behavioral seizure stage (BSS) of each induced seizure in the initial stage of kindling; the kindling rates for stage 3 and stage 5 seizures; seizure parameters at the completion of kindling of the drug-treated groups were recorded and compared to the values of each saline-treated control group. Our result showed that MK-801 administration prior to each electrical stimulation selectively and significantly increased PNT in the initial stage of kindling without affecting other seizure parameters. Chronic pretreatment of MAP caused a selective and significant decrease of PNT of the first two stimulations in the kindling process. Taken together with the previous studies, these results suggest that long-term potentiation plays an important role in the development of the excitability of seizure focus but not of the induced seizure's propagation in the hippocampal kindling phenomenon. Clinically MK-801 seems to be a more efficacious drug in preventing the induction of seizures than in suppressing the acquired seizures.

Animals↗

PubMed1992

Antiepileptic effects of MK-801, a noncompetitive NMDA-receptor antagonist, in the low-frequency kindling model of epilepsy.

We assessed the acute effect of MK-801 (0.05-0.7 mg/kg), a noncompetitive NMDA-receptor antagonist, on hippocampus-kindled seizures induced with low-frequency (2 Hz) electrical stimulations. MK-801 dose-dependently increased the seizure threshold (PNT, the number of stimulating pulses required for the triggering of epileptic after discharge), whereas most of the previous studies which assessed the effect of MK-801 on kindled seizures could not detect the elevation of seizure threshold by MK-801. In addition MK-801 decreased the severity of induced seizures at low doses at which previous studies could not detect the antiepileptic effect of MK-801, suggesting that the low-frequency kindling technique might be a more sensitive and reliable model of epilepsy than the conventional high-frequency kindling technique.

Animals↗

PubMed1991

Two types of neuroplasticities in the kindling phenomenon.

We stimulated the dorsal hippocampus of the rat with 2 Hz electrical stimulation to induce kindling seizures. As we reported previously using cats, pulse-number threshold (PNT), the number of stimulating-pulses required for the triggering of epileptic afterdischarge, decreased profoundly in the initial stage of the kindling process and the behavioral seizure stage (BSS) developed in the later stage. After the completion of kindling, a 4 week interval elevated PNT significantly compared to the value at the completion of kindling, whereas BSS showed no regression. These results suggest that there are two types of neuroplasticities which are independent of each other in the kindling phenomenon, one is the early-short type which is involved in the susceptibility of epileptic focus in hippocampus and the other is the late-long type which is involved in the full propagation of kindled seizures to the extra-limbic area.

Animals↗

PubMed1991

Effects of chronic treatment with haloperidol and methamphetamine on hippocampal kindled seizures in the cat.

We assessed the effects of chronic treatment with haloperidol (0.5-2 mg/kg/day, p.o., 17 days) and methamphetamine (1-2 mg/kg/day, p.o., 17 days; 4 mg/kg/day, p.o. 9 days) on hippocampal kindled seizures using a kindling procedure with low-frequency (about 3 Hz) electrical stimulation in cats. The number of stimulating pulses required to trigger epileptic afterdischarge (pulse-number threshold, PNT) was considered an indicator of seizure threshold. Haloperidol, 0.5 and 1.0 mg/kg, reduced the duration of epileptic afterdischarge (afterdischarge duration, ADD) without affecting PNT, and 2.0 mg/kg strongly reduced PNT and ADD. Methamphetamine, 2.0 mg/kg, reduced PNT and ADD, and 4.0 mg/kg preferentially reduced PNT. The effects of the two drugs on hippocampal kindled seizures were found to be partially opposite to those on amygdala kindled seizures, suggesting the different response of these limbic structures to dopamine receptor manipulation.

Animals↗

PubMed1990

Effects of anticonvulsants on hippocampus-generating seizures.

Acute effects of 4 anticonvulsants on hippocampal kindled seizures induced with about 3 Hz electrical stimulations were assessed in cats. The number of stimulating pulses required for the triggering of epileptic afterdischarge (pulse-number threshold, PNT) was used as the indicator for the seizure threshold. Duration of afterdischarge (ADD), ictal and interictal behaviors and serum drug levels were also recorded. PB produced a PNT-increase more prominently than an ADD-decrease with seizure stage regression. PHT produced only a proconvulsive effect by decreasing PNT. CBZ also produced a proconvulsive effect by decreasing PNT at a low dose, and decreased PNT and ADD simultaneously at a high dose. Conversely VPA increased PNT and ADD simultaneously. These results were discussed comparing mainly with a previous study of amygdala-generating seizures.

Animals↗

PubMed1990

A biphasic change of afterdischarge threshold during the kindling process.

Cats were stimulated in the ventral hippocampus with low-frequency (about 3 Hz) square wave pulses. All subjects were kindled until generalized convulsion occurred. During the kindling process, the number of stimulating pulses required for the provocation of afterdischarge (AD), which was used as an indicator of AD threshold, decreased suddenly in the initial stage and increased gradually in the late stage. We consider this phenomenon to be important in deepening the understanding of seizure generation.

Action Potentials↗

PubMed1989

An evidence of 'post-seizure excitation' in feline-kindled seizures.

We assessed the post-seizure effects on the seizure threshold and the seizure duration using low-frequency kindling technique. The number of stimulating pulses required for a triggering of epileptic afterdischarge (pulse-number threshold; PNT) was used for the indicator of seizure threshold. PNT increased significantly at 2 and 4 h inter-stimulation intervals, whereas it decreased significantly with an increase of seizure duration at 16 and 24 h intervals. It appears from these data that a post-seizure excitation occurs after a post-seizure inhibition.

Action Potentials↗

PubMed1989

[A biphasic changes in the seizure-threshold in kindling seizure development induced with low-frequency electrical stimulations].

Seven cats were stimulated once a day with low-frequency electrical stimulations to assess the serial changes of development. Each animal had been implanted stereotaxically with a stimulating electrode into the left-side ventral hippocampus and with recording electrodes into the right-side ventral hippocampus, the bilateral dorsal hippocampus. We applied the stimulations at 10:00 AM, bipolarly with 2 mA-biphasic square-wave pulses (1 msec durations). The pulse-interval was set at 300 msec. If epileptic afterdischarge could not be triggered on EEG with this pulse-interval, a 100msec-interval stimulation was applied after 15 min-rest period. The number of stimulating pulses required for a triggering of afterdischarge was defined as pulse-number threshold (PNT) which was used as an indicator of the seizure-threshold. The duration of each seizure on EEG (afterdischarge duration, ADD) was also recorded and the seizure-related behaviors were classified into 5 stages as follows: 1, staring or immobility; 2 appearance of facial twitching or head nodding ; 3, tonic convulsions of the right-side fore-paw or a head turning toward the right-side; 4, generalized clonic convulsions; 5, generalized convulsions with a falling down. The kindling procedure completed within a mean of 36.5 days, and all the animals presented stage-5 seizures. At the completion of kindling, PNT was determined at 10.5 +/- 1.8 (mean +/- SE). During the kindling process PNT showed a sudden decrease in the initial part of stage-1 (within a mean of 3.8 days) and a gradual increase from stage-3 to stage-5. ADD showed a simple increasing function of the development of seizure-stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

[Effects of phenobarbital and phenytoin on hippocampus generating seizures].

We have recently reported some pharmacological studies using a kindling model of epilepsy induced with 1-3 HZ electrical stimulations, referred to as the low-frequency kindling. Since a previous study showed that the effects of psychotropic drugs on limbic seizures were dependent on the location of epileptic focus, we decided to study acute and chronic effects of anticonvulsants on the hippocampus generating seizures to compare with the results of a previous study of the amygdala generating seizures, which was done under the same conditions with this study. The number of stimulating pulses required for the triggering of epileptic afterdischarge (pulse-number threshold) was used as the indicator for the seizure threshold. Duration of after discharge (ADD), ictal and interictal behaviors of the subjected 7 cats, and serum drug levels were also recorded. A dose-dependent increase of serum drug levels was confirmed in each drug, and the values were well comparable with the optimal range in clinical use. In acute experiment PB 5 mg/kg p.o. produced no significant effect on PNT and ADD. PB 10 mg/kg increased PNT significantly (p less than 0.02) at 2 hrs after administration without affecting ADD, but 4 cats presented the seizure-stage regressions. PB 20 mg/kg increased PNT (p less than 0.02) and decreased ADD (p less than 0.02) with the seizure-stage regressions of all the tested cats at 2 hrs after administration, and increased PNT (p less than 0.05) without affecting ADD and seizure stage at 96 hrs after administration. PHT 5, 10, 20 mg/kg decreased PNT (p less than 0.05, 0.02, 0.02, respectively) without affecting ADD at 2 hrs after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

PubMed1988

Effects of chronic lithium treatment on limbic seizure generation in the cat.

The effect of chronic lithium administration (2.2-8.7 mEq/kg/day, 17 days) to the cat on seizure initiation in the amygdala and hippocampus was assessed by the low-frequency kindling technique. Lithium 4.3 mEq/kg/day PO, producing a serum lithium level between 1.2 and 1.6 mEq/l, caused an elevation of the amygdala seizure threshold on treatment days 5-9. In contrast, the same dosage caused a transient reduction of the hippocampus seizure threshold on treatment days 13-17 and on withdrawal days 21-25. Lithium 2.2 mEq/kg/day PO caused no significant effect on the parameters of the two types of seizure. Lithium 8.7 mEq/kg/day PO caused severe behavioral changes and did not permit chronic treatment. These results indicate that the effect of chronic lithium treatment on limbic seizures is dependent on the location of epileptic focus.

Animals↗

PubMed1988

Effects of chronic treatment of methamphetamine and imipramine on amygdaloid seizure's generation.

We assessed the effects of chronic treatment of methamphetamine (1-2 mg/kg/day, i.p., 17 days) and imipramine (2-8 mg/kg/day, p.o., 17 days) on amygdala-generating seizures using the kindling method induced by low-frequency electrical stimulations. The number of stimulating pulses required for the triggering of epileptic afterdischarge (pulse-number threshold: PNT) is the indicator of seizure generating threshold. A PNT elevation followed by its reduction occurred, compared to the pretreatment level, during a 2 mg/kg/day chronic methamphetamine treatment. A reduction in the PNT and triggered afterdischarge durations occurred during a chronic imipramine treatment. These results indicate that both methamphetamine and imipramine reduced the seizure generating threshold by repeated applications. It is suggested that this finding might be related to the psychoactive potency and associated neurochemical changes which are known to be caused by these drugs.

Amygdala↗

PubMed1985

Granuloma formation by muramyl dipeptide associated with branched fatty acids, a structure probably essential for tubercle formation by Mycobacterium tuberculosis.

Muramyl dipeptide, which does not induce epithelioid granuloma when injected alone dissolved in phosphate-buffered saline, could induce extensive granulomas in guinea pigs when chemically conjugated with branched, but not linear, fatty acids. Peptidoglycan fragments of Staphylococcus epidermidis could evoke epithelioid granulomas when incorporated in a water-in-oil emulsion. These findings suggest the importance of a lipid bound to muramyl dipeptide for granuloma formation. In view of the fact that mycobacteria uniquely contain large amounts of branched fatty acids, it was proposed that the complex of muramyl dipeptide and branched fatty acids, mostly mycolic acids, is a structure in tubercle bacilli responsible for tubercle formation.

Acetylmuramyl-Alanyl-Isoglutamine↗