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PubMed1992

A post-synaptic depressant modulatory action of 5-hydroxytryptamine on excitatory amino acid responses in rat entorhinal cortex in vitro.

The depressant action of 5-hydroxytryptamine (5-HT) in slices of entorhinal cortex of the rat has been examined. When single intracellular recordings of pyramidal cells in layers II/III of entorhinal cortex of the rat were made and drugs applied by iontophoresis, 5-HT evoked virtually no changes in passive membrane properties of the majority of cells studied. When short regular pulses of glutamate were applied to the neurones and 5-HT was ejected in addition, the depolarisations caused by glutamate were considerably reduced in amplitude. This attenuation persisted in medium containing cadmium chloride (200 microM) to block synaptic transmission. The magnitude of the response to 5-HT was dependent on the ejection current and this effect could not be mimicked by increasing ejections of Na+ or H+ ions. 5-Hydroxytryptamine had no apparent action on neuronal responses to iontophoretically ejected gamma-amino butyric acid (GABA). In later studies, the action of 5-HT was examined on epileptiform discharges, evoked in the presence of the GABA antagonist, bicuculline, in the same group of cells. Droplet application of 5-HT into the recording chamber, or perfusion of 10 microM 5-HT regularly attenuated the length of epileptiform bursts but, at this concentration, had no discernible effect on the resting membrane potential or membrane input resistance. The effect of 5-HT on the release of glutamate from slices of entorhinal cortex has also been examined using a fluorometric enzyme assay. Concentrations of 5-HT as large as 30 microM had no effect on the release of endogenous glutamate in these experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[The entorhinal cortex (hippocampal formation) in aging and Alzheimer's disease. Neuroanatomical interpretation].

This paper deals with the neuronal changes shown by the entorhinal cortex in aging (30 cases) and in Alzheimer's disease (17 cases). In both instances, changes show a neuronal loss (measured as an index of cortical atrophy). The entorhinal cortex more closely related to polymodal association cortex hardly shows any variation with age, while Alzheimer cases present very intense neuronal loss. This pattern is interpreted taking into account the present knowledge about the connectivity of the entorhinal cortex and the remainder of the hippocampal formation and their role in memory processing.

Adolescent↗
PubMed1985

The effects of entorhinal cortex lesions on type 1 and type 2 theta.

The effects of bilateral entorhinal cortex lesions on type 1 and type 2 theta generation in the guinea pig were studied in the chronic preparation. EEG recordings from dentate generator zones demonstrated a decrease in the relationship between ongoing type 1 motor movements and theta generation. Before lesioning theta activity accompanied type 1 behaviors (i.e., walking and head movements) in 100% of the samples, while subsequent to lesioning theta activity was present in only 58% of the samples. In addition, prior to lesioning, type 2 theta was present in 100% of the samples taken during immobile sensory processing, e.g., tactile stimulation, while after lesioning type 2 theta was present in only 34% of the samples. Type 2 theta is selectively sensitive to disruption by atropine sulfate. In the present experiment atropine sulfate eliminated all theta activity after entorhinal lesions. Consequently as no type 1 theta appeared to be present it was argued that the entorhinal cortex is a critical route for type 1 theta. However, as the behavioral and sensory correlates of both type 1 and type 2 theta were disrupted it was suggested that the entorhinal cortex is an integral part of both systems.

Animals↗
PubMed1998

Entorhinal cortex of the rat: topographic organization of the cells of origin of the perforant path projection to the dentate gyrus.

By using three-dimensional computer reconstruction techniques and the production of two-dimensional unfolded maps, we analyzed the topographic organization of projections from the entorhinal cortex of the rat to the dentate gyrus. The retrograde tracers, Fast blue and Diamidino yellow, were injected at all septotemporal levels of the dentate gyrus, and the distribution of retrogradely labeled layer II cells in the entorhinal cortex was plotted by using computer-aided microscopy systems. Discrete injections of fluorescent dyes into the dentate gyrus labeled bands of layer II neurons in the entorhinal cortex that covered approximately 45% of its surface area. Injections confined to the septal half of the dentate gyrus resulted in a band that occupied the most lateral and caudomedial portions of the entorhinal cortex. Although there were subtle changes in the density of labeled cells in this region, essentially the same region of cells was labeled after any injection into the septal half of the dentate gyrus. Injections into mid-septotemporal levels of the dentate gyrus (50-75% of the distance from the septal pole) led to a distinctly different pattern of retrograde labeling. A more medial portion of the lateral entorhinal cortex and a more rostral portion of the medial entorhinal area were labeled in these cases. Another change in entorhinal labeling occurred when the injection involved the most temporal quarter of the dentate gyrus. Injections into this area led to a constrained region of entorhinal labeling that included the most medial portion of the lateral entorhinal area and the most rostral portion of the medial entorhinal area. Although the domains of cells projecting to septal, mid-septotemporal, and temporal levels of the dentate gyrus were not entirely segregated, there was relatively little overlap of the three populations of neurons. These data raise the possibility that different portions of the entorhinal-hippocampal circuit are capable of semiautonomous information processing, at least at the stage of input to the dentate gyrus.

Amidines↗
PubMed2002

Associative interactions within the superficial layers of the entorhinal cortex of the guinea pig.

Associative fiber systems in the entorhinal cortex (EC) have been extensively studied in different mammals with tracing techniques. The largest contingent of intra-EC cortico-cortical fibers runs in the superficial layers and is distributed predominantly within longitudinal cortical bands. We studied the patterns of intrinsic EC connectivity in the in vitro isolated guinea pig brain preparation by performing current-source density analysis of field potential laminar profiles recorded with multi-channel silicon probes. The response pattern evoked by stimulation of the lateral olfactory tract was utilized to identify the lateral (l-EC) and medial (m-EC) entorhinal cortex. Stimulation of the deep layers did not evoke consistent responses. Local stimulation of the superficial layers in different portions of the EC induced an early, possibly direct response restricted to layer II-III in the close proximity to the stimulating electrode, followed by a late potential in the superficial layer I, that propagated at distance with a progressively increasing latency. The monosynaptic nature of the delayed response was verified by applying a pairing test. The results demonstrated that stimulation in the rostral-medial part of the EC generated activity restricted to the rostral pole of the l-EC, stimulation of the m-EC induced an associative activation that propagated rostrocaudally within the m-EC, stimulation of the caudal pole of the m-EC induced an additional response directed laterally, and stimulation of the lateral band of the EC determined a prominent longitudinal propagation of neuronal activity, but also induced associative potentials that propagated medially. The results are in partial agreement with the general picture derived from the anatomical studies performed in different species. Even though the largest associative interactions between superficial layers are restricted within either the m-EC or the l-EC, both rostral and caudal stimuli in the EC region close to the rhinal sulcus induced activity that propagated across the border between l- and m-EC.

Action Potentials↗
PubMed2002

Caspase-3-associated apoptotic cell death in excitotoxic necrosis of the entorhinal cortex following intraperitoneal injection of kainic acid in the rat.

The present study is directed to study: (a) bax translocation and cytochrome c release as mediators of the mitochondrial pathway of apoptosis; (b) Fas-L (Fas-ligand) expression as an indicator of the possible involvement of the Fas/Fas-L signaling pathway; and (c) active caspase-3 expression as the main executioner of caspase-mediated apoptosis, in rats receiving an intraperitoneal injection of the glutamate analogue kainic acid (KA) at a dose of 9 mg/kg, which is sufficient to produce generalized seizures and excitotoxic cell death in the entorhinal cortex. Sub-fractionation studies of entorhinal cortex homogenates have shown cytochrome c and cytochrome oxidase IV localized in the mitochondrial fraction, and Bax localized in the cytosolic fraction. No modifications in the sub-cellular distribution of cytochrome c and Bax have been observed at 6 h and 24 h in KA-treated rats. Morphological studies have shown cytoplasmic shrinkage and nuclear condensation consistent with necrosis in the entorhinal cortex. Many neurons (about 30% of dying cells) are stained with the method of in situ end-labeling of nuclear DNA fragmentation. Yet only about 5% of dying cells have apoptotic morphology. A percentage of dying cells (5% at 6 h and 40% at 24 h) over-express Fas-L but only about 2% of dying cells at 24 h post-injection express cleaved caspase-3 (17 kD). The present data further support the concept that necrosis is the predominant form of cell death in the entorhinal cortex, although caspase-3-dependent apoptotic cell death may play a limited role, in the present paradigm of KA-induced excitotoxicity.

Animals↗
PubMed2000

Selective lesions of the entorhinal cortex, the hippocampus, or the fimbria-fornix in rats: a comparison of effects on spontaneous and amphetamine-induced locomotion.

Using adult Long-Evans male rats, this experiment compared spontaneous (assessed 15 days and 4.5 months after surgery) and amphetamine-induced (assessed from 4.5 months after surgery onwards; 1 mg/kg, i.p., ten injections, 48 h apart) locomotor activity following N-methyl-D-aspartate lesions of the entorhinal cortex, electrolytic lesions of the fimbria-fornix, or ibotenate lesions of the hippocampus. Sham-operated rats were used as controls. Hippocampal and fimbria-fornix lesions, but not entorhinal-cortex lesions induced diurnal and nocturnal hyperactivity, which was attenuated over time, but only in rats with fimbria-fornix lesions. Amphetamine-induced hyperlocomotion was assessed in a familiar environment. Lesions of the entorhinal cortex potentiated the locomotor effects of amphetamine, but not lesions of the hippocampus or interruption of the axons in the fimbria-fornix pathway. Sensitization appeared to be decreased by fimbria-fornix lesions and to be prevented by hippocampal lesions. Rats with entorhinal-cortex lesions behaved as if they had already been sensitized by the lesion. These results clearly show that lesions of the fimbria-fornix, the hippocampus, and of the entorhinal cortex have different effects on spontaneous and amphetamine-induced hyperactivity, as they also have on learning and memory tasks.

Amphetamine↗
PubMed1998

Serotonin reduces synaptic excitation in the superficial medial entorhinal cortex of the rat via a presynaptic mechanism.

1. The superficial layers II and III of the entorhinal cortex, which form the main cortical input to the hippocampus, receive a large serotonergic projection from the raphe nuclei and express 5-HT receptors at high density. Here, we studied the effects of serotonin on the intrinsic properties and excitatory synaptic transmission of the superficial medial entorhinal cortex. 2. Intracellular and patch clamp recordings revealed that serotonin hyperpolarized only one-third of the cells, approximately, through a potassium conductance via a GTP-dependent process. 3. Serotonin depressed mixed as well as isolated alpha-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid receptor (AMPAR)- and N-methyl-D-aspartic acid receptor (NMDAR)-mediated excitatory postsynaptic potentials/currents (EPSPs/EPSCsapproximately 40 % reduction with 1 microM serotonin). 4. The effect of serotonin on EPSPs/EPSCs was similar in whole-cell versus intracellular recordings; it did not require intracellular GTP and was not visible in glutamate applications to excised patches. Miniature EPSCs recorded in the presence of tetrodotoxin and bicuculline were reduced in frequency, but not altered in amplitude. 5. The effects of serotonin on intrinsic properties and EPSPs were partially mimicked by 5-HT1A receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) and 5-carboxamido-tryptamine maleate (5-CT), and reduced by 5-HT1A receptor antagonists S-(-)-5-fluoro-8-hydroxy-DPAT hydrochloride (S-UH-301), 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide (NAN-190) and spiperone. 6. We conclude that serotonin potently suppresses excitatory synaptic transmission via 5-HT1A receptors in layers II and III of the medial entorhinal cortex by a presynaptic mechanism.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Methylazoxymethanol acetate-induced abnormalities in the entorhinal cortex of the rat; parallels with morphological findings in schizophrenia.

It has been suggested repeatedly that the non-heritable factors in the pathogenesis of schizophrenia involve abnormalities of prenatal neurodevelopment. Furthermore, post-mortem studies show neuropathology of apparently developmental origin in the entorhinal cortex and other brain regions of schizophrenic subjects. In an attempt to model a developmental defect of the entorhinal region in the rat, cerebrocortical proliferation was briefly interrupted during its earliest stages, when the entorhinal area is thought to undergo major cell division. Specifically, the experimental set-up involved the administration of methylazoxymethanol acetate (MAM) on 1 of 4 consecutive days of embryonal development, from E9 to E12. Analysis of the forebrain in adult animals shows reduction of the entorhinal cortex in rats treated on each of these days. This effect shifts from lateral to medial divisions of the entorhinal cortex with later administration of MAM, following a known developmental gradient. Morphological consequences of MAM administration appear to be largely confined to the entorhinal cortex in the groups treated on E9 to E11, although slight reductions of the frontal and occipital neocortex were also observed in these animals. MAM treatment on E12 produces relatively more widespread damage, as reflected among other in a small reduction of brain weight. The described brain abnormalities are not accompanied by obvious phenotypical changes in any, but the E12-treated group. They, moreover, involve cortical thinning, disorganised cortical layering, and abnormal temporal asymmetries. These finding bare some similarity to observations in brains of schizophrenic subjects. The possible relevance of this approach in modeling neurodevelopmental aspects of schizophrenia is discussed.

Animals↗
PubMed1998

Downregulation of oxidative phosphorylation in Alzheimer disease: loss of cytochrome oxidase subunit mRNA in the hippocampus and entorhinal cortex.

Messenger RNA (mRNA) for cytochrome oxidase subunit II (COX II) was localized by in situ hybridization in the entorhinal cortex and hippocampal formation of postmortem brain tissue from normal human subjects and from patients with Alzheimer disease (AD). In the control entorhinal cortex, COX II mRNA was detected mainly in neuronal cell bodies of layers II and IV. In control hippocampal formation, highest levels were localized in neuronal cell bodies of the dentate gyrus and the CA3 and CA1 regions, neurons that are involved in the major input and output pathways of the hippocampal formation. In AD brain, COX II mRNA was markedly reduced in the entorhinal cortex and the hippocampal formation compared with control brain. In the AD hippocampal formation, reductions were in regions severely affected by AD pathology as well as in regions that were relatively spared. These results are consistent with the hypothesis that reduced mitochondrial energy metabolism reflects loss of neuronal connections in AD.

Aged↗
PubMed1997

Cytoarchitecture of the entorhinal cortex in schizophrenia.

OBJECTIVE: The purpose of this study was to determine whether schizophrenia is associated with abnormalities in neuronal migration in the entorhinal cortex. METHOD: Nissl-stained sections through three cytoarchitectonic subdivisions of the entorhinal cortex were examined in postmortem brain specimens from 10 schizophrenic subjects and 10 matched normal comparison subjects. RESULTS: No qualitative differences in cytoarchitecture were observed between the schizophrenic and comparison subjects. CONCLUSIONS: These findings do not replicate previous reports of cytoarchitectural disturbances in the entorhinal cortex of schizophrenic subjects and thus fail to support the hypothesis of abnormal neuronal migration in schizophrenia.

Entorhinal Cortex↗
PubMed1997

Dopamine efflux in the rat nucleus accumbens evoked by dopamine receptor stimulation in the entorhinal cortex is modulated by oestradiol and progesterone.

This study compared the effects of dopamine receptor stimulation in the entorhinal cortex on dopamine release in the nucleus accumbens, measured by in vivo microdialysis in conscious Sprague-Dawley rats, with and without oestradiol and progesterone priming. Nonselective dopamine receptor stimulation with apomorphine reduced dopamine release in the nucleus accumbens, an effect which was prevented by injection of cis-flupenthixol into the entorhinal cortex. Selective D1 receptor stimulation with SKF38393 increased dopamine release, whereas selective D2 receptor stimulation with quinpirole did not affect dopamine release. Combined administration of oestradiol and progesterone potentiated the response to apomorphine and prevented the response to SKF38393. The effects of single hormone administration on the response to apomorphine suggested that the modulation was primarily due to oestradiol enhancing effects of progesterone. Experiments with high [K+] suggested these hormonal effects were exerted predominantly in the entorhinal cortex. The present experiments have demonstrated that dopaminergic modulation of transmission in a cortico-striatal loop linking temporal and prefrontal cortex is regulated by oestradiol and progesterone. Dysfunction in this system in humans may give rise to affective and cognitive symptoms which may, if initiated by a postpartum fall in oestrogen and progesterone concentrations, constitute the core pathophysiology of puerperal psychosis.

Animals↗
PubMed2002

Activation of neurokinin-1 receptors promotes GABA release at synapses in the rat entorhinal cortex.

We have previously shown that activation of neurokinin-1 receptors reduces acutely provoked epileptiform activity in rat entorhinal cortex in vitro, and suggested that this may result from an increase in GABA release from inhibitory interneurones. In the present study we have made whole cell patch clamp recordings of spontaneous GABA-mediated inhibitory postsynaptic currents as an indicator of GABA release in slices of rat entorhinal cortex, and determined the effects of neurokinin receptor activation on this release. The neurokinin-1 receptor agonists septide and GR73632 provoked a robust increase in the frequency of GABA-mediated currents, and an increase in mean amplitude. The effects were mimicked by substance P, and blocked by a neurokinin-1 receptor antagonist. High concentrations of neurokinin A had similar effects, which were also blocked by the neurokinin-1 receptor antagonist, but agonists at neurokinin-2 or neurokinin-3 receptors were ineffective. The increases in amplitude and frequency of events provoked by septide were prevented by prior blockade of action potential-dependent release with tetrodotoxin. In current clamp recordings from putative interneurones, GR73632 evoked depolarisation and a prolonged discharge of action potentials. Finally, recordings from pyramidal neurones and oriens-alveus interneurones in CA1 of the hippocampus showed that application of GR73632 caused an increase in frequency and amplitude of GABA-mediated inhibitory postsynaptic currents in the former and persistent firing of action potentials in the latter. The results demonstrate that neurokinin-1 receptor activation promotes the release of GABA at synapses on principal neurones in both entorhinal cortex and hippocampus. The abolition of this effect by tetrodotoxin and the excitatory responses seen in interneurones clearly suggest that the neurokinin-1 receptor is localised on the soma-dendritic domain of the inhibitory neurones. Thus, substance P inputs to inhibitory neurones may have a widespread influence on cortical network excitability and could play a role in epileptogenesis and its control.

Animals↗
PubMed2006

Cooperation between the hippocampus and the entorhinal cortex in spatial memory: a disconnection study.

It has been recently shown that lesions of parahippocampal areas including the entorhinal cortex do not disrupt place learning in the water maze, suggesting that the hippocampo-cortical circuitry is not important for spatial memory [Burwell RD, Saddoris MP, Bucci DJ, Wiig KA. Corticohippocampal contributions to spatial and contextual learning. J Neurosci 2004;24:3826-36]. The aim of the present study was to tax more directly the cooperation between the hippocampus and entorhinal cortex in two different spatial tasks, a place navigation task and a spontaneous object exploration task, using a disconnection procedure. Damaging the entorhinal-hippocampal system induced impairments in the two tasks but only in the spatial object exploration task rats with contralateral lesions displayed a greater deficit than rats with ipsilateral lesions. The results suggest that the cooperation between the hippocampus and the entorhinal cortex is modulated by the nature of the task and the cognitive processes involved in formation of spatial memory.

Animals↗
PubMed2005

The entorhinal cortex regulates blood glucose level in response to microinjection of neostigmine into the hippocampus.

OBJECTIVE: Microinjectin of neostigmine, an inhibitor of acetylcholine esterase, into the rat hippocampus elicited stress-like responses reflected by the release of adrenocorticotropic hormone (ACTH) and blood glucose elevations. The entorhinal cortex is regarded as an interface between the hippocampus and neocortex. The current study was designed to examine the role of the entorhinal cortex in regulation of blood glucose elevation induced by hippocampal neostigmine injection. MATERIAL AND METHODS: We produced the entorhinal cortex lesions in 9 week-old male Wistar rats by the bilateral injections of the cell-selective neurotoxin, ibotenic acid (15microg/microl). Two weeks after the injections, neostigmine methylsulfate (sigma, 5x10(-8) mol) was microinjected into the rat hippocampus in a volume of 1microl for 1min using a CMA/100 microinjection pump. Plasma ACTH levels were measured by radioimmunoassay. Plasma glucose concentrations were determined by the immobilized enzyme membrane/H2O2 method with a compact glucose analyzer Antsense II (Bayer Medical Co.Ltd,Tokyo, Japan). RESULTS: Compared with sham-operated control rats, the entorhinal lesions produced by ibotenic acid significantly attenuated the elevations of blood glucose evoked by the microinjection of neostigmine into the hippocampus. However, no significant difference of plasma ACTH in response to the injection was observed between the entorhinal-lesioned rats and controls. CONCLUSION: The results of the present study indicate that the entorhinal cortex plays a role in the central nervous systems regulation of blood glucose and may be involved in a stress response presumably via an alternative pathway.

Animals↗
PubMed2002

Immunohistochemical localization of GABAB receptor in the entorhinal cortex and inferior temporal cortex of schizophrenic brain.

Immunocytochemical techniques were employed to examine the changes in immunolabeling of the gamma-aminobutyric acid (GABA)B receptor within the entorhinal cortex and inferior temporal isocortex of the schizophrenic brain. In the entorhinal cortex of the control subjects, an intense immunoreactivity was observed in the soma and processes of stellate cells in Layer II, in pyramidal cells in Layers II, III, and V, and in nonpyramidal interneurons. In subjects with schizophrenia, GABA(B) immunoreactivity was markedly reduced in pyramidal cells throughout the layers. In the inferior temporal cortex of the controls, both pyramidal cells and nonpyramidal interneurons demonstrated an intense immunoreactivity, while in the same region of the schizophrenic brain a marked reduction of the GABA(B) immunolabeling was observed in pyramidal cells in Layer V. These findings suggest that in the entorhinal cortex and the inferior temporal cortex of the schizophrenic brain, the expression of the GABA(B) receptor is reduced, and raise the possibility that GABA(B) receptor dysfunction is involved in the pathophysiology of schizophrenia.

Aged↗
PubMed1999

Comparative MR analysis of the entorhinal cortex and hippocampus in diagnosing Alzheimer disease.

BACKGROUND AND PURPOSE: Our purpose was to use volumetric MR imaging to compare the extent of atrophy and discriminative ability of the volumes of two temporal lobe structures, the entorhinal cortex and the hippocampus, between patients with Alzheimer disease and control subjects. METHODS: The study group consisted of 30 patients with probable Alzheimer disease diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and 32 healthy control subjects. The MR volumes of the entorhinal cortex and the hippocampus were used for the discriminant function and receiver operator characteristic analysis as well as multivariate analysis of variance for repeated measures to compare their discriminative power. RESULTS: Compared with control subjects, patients with Alzheimer disease had significantly smaller volumes of the entorhinal cortex and the hippocampus on both sides. Both the receiver operator characteristic and the discriminant function analyses using both volumes classified control subjects and Alzheimer patients with a high degree of accuracy (approximately 90%). Significant group x region interaction favoring hippocampal volumetry was determined by multivariate analysis of variance. CONCLUSION: The volumetric measurements of both the entorhinal cortex and hippocampus have comparably high discriminative power in diagnosing Alzheimer disease. In clinical practice, hippocampal volumetry may be more feasible, because the method is easier to use and has less variability.

Aged↗
PubMed1997

Effects of AWD 140-190 on stimulus-induced field potentials and on different patterns of epileptiform activity induced by low calcium or low magnesium in rat entorhinal cortex hippocampal slices.

AWD 140-190 a potent new anticonvulsant was tested on several types of epileptiform activities in entorhinal cortex hippocampal slices. AWD 140-190 suppressed completely and in a dose-dependent manner spontaneous seizure-like events induced by lowering extracellular Ca2+. In the low magnesium model, AWD 140-190 applied with 200 microM reduced recurrent short discharges in area CA1 by 48.1 +/- 14.7%, while in the entorhinal cortex seizure-like events were not depressed. Late recurrent discharges were increased in frequency to 213.8 +/- 78.1 and reduced in amplitude by 50.1 +/- 14.4%. Responses to paired pulse stimuli with intervals ranging from 20 to 150 ms were reduced both with alvear and stratum radiatum stimulation. Decreases in [Ca2+]0 and associated slow field potentials evoked by repetitive stimulation of stratum radiatum were also depressed in a dose-dependent manner. AWD 140-190 also reduced stimulus-induced rises in [K+]0. AWD 140-190 200 microM diminished the amplitude of slow field potentials observed during high K(+)-induced spreading depression by about 17% in CA1 and 34% in entorhinal cortex without any significant effect on SD-associated rises in [K+]0. These results suggest that AWD 140-190 has an anticonvulsant effect presumably by interfering with repetitive generation of action potentials. AWD 140-190 may also possess modulatory effects on glial cells as suggested by the strong depression of SD-associated slow negative potential shifts.

Animals↗