Changes in cortical amino acids during electrical kindling in rats

Leach, Michael J.; Marden, Caroline M.; Miller, A A; O'Donnell, R.A.; Weston, Shane B

doi:10.1016/0028-3908(85)90118-2

Cited by 39 publications

(2 citation statements)

References 14 publications

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“…Veratridine-Induced Glutamate Release. The assay followed procedures reported , with some modifications. Cross-chopped slices, 0.2 mm thick, from rat brain cortex or striatum (strain Chbb:Thom) were prepared and preincubated at 37 °C for 45 min in Krebs−Henseleit buffer (in mM: NaCl 120, KCl 4.8, CaCl 2 1.3, KH 2 PO 4 1.2, MgSO 4 1.2, NaHCO 3 25, pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Structure−Activity Relationships of 6,7-Benzomorphan Derivatives as Use-Dependent Sodium Channel Blockers for the Treatment of Stroke

et al. 2002

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We have synthesized a series of 6,7-benzomorphan derivatives and determined their ability to bind to voltage-dependent sodium channels. We have also compared the functional consequences of this blockade in vitro and in vivo. The ability of the compounds to displace [(3)H]batrachotoxin from voltage-dependent sodium channels was compared with their ability to inhibit [(3)H]glutamate release in rat brain slices and block convulsions in the maximal electroshock test in mice. We found that the hydroxyl function in the 4'-position is crucial for improving the sodium channel blocking properties. Moreover, the stereochemistry and the topology of the N-linked side chain also influence this interaction. Indeed, the affinity is improved by an aromatic substitution in the side chain. By modifying the N substituent and the substitution pattern of the hydroxyl function, we were able to discover (2R)-[2alpha,3(S),6alpha]-1,2,3,4,5,6-hexahydro-6,11,11-tri-methyl-3-[2-(phenylmethoxy)propyl]-2,6-methano-3-benzazocin-10-ol hydrochloride. This compound was chosen as the best candidate for further pharmacological investigations.

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Section: Methodsmentioning

confidence: 99%

Synthesis and Structure−Activity Relationships of 6,7-Benzomorphan Derivatives as Use-Dependent Sodium Channel Blockers for the Treatment of Stroke

et al. 2002

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“…Assessment of the neurochemistry of epilepsy typically has examined glutamate, aspartate, GABA and the monoamines. Although, daily kindling invariably results in heightened behavioral and physiological excitation (and/or reduced inhibition), this increase in excitability is frequently but not always associated with a concomitant increase of glutamate and decrease in GABA levels near the site of activation (Leach et al ., 1985; Goren et al ., 2003). Presently we question whether such a profile of neurotransmitter availability is always associated with epileptogenesis, and is similarly witnessed during an MS procedure, where variable epileptogenesis is evident, depending upon the animal's genetic background.…”

Section: Introductionmentioning

confidence: 99%

Amygdala amino acid and monoamine levels in genetically Fast and Slow kindling rat strains during massed amygdala kindling: a microdialysis study

Shin

Anisman

Merali

et al. 2004

Eur J of Neuroscience

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We investigated the neurochemistry of epileptic seizures in rats selectively bred to be seizure-prone (Fast) vs. seizure-resistant (Slow) to amygdala kindling. Microdialysis was used to measure levels of amino acids [glutamate, aspartate and gamma-aminobutyric acid (GABA)] and monoamines (noradrenaline, dopamine and serotonin) during 'massed' stimulation (MS) (every 6 min) of the ipsilateral amygdala for a total of 40 stimulation trials. Behavioral seizure profiles together with their afterdischarge thresholds (ADTs) and associated durations were assessed during the procedure, and subsequently were redetermined 1, 7 and 14 days later. Then normal 'daily' kindling commenced and continued until the animal reached the fully kindled state. During MS, several generalized seizures were triggered in Fast rats that were associated with long afterdischarge (AD) durations and intermittent periods of elevated thresholds, but in Slow rats, most stimulations were associated with stable ADTs and short ADs. Progressively increasing extracellular glutamate and decreasing GABA was observed in Fast rats during the MS, whereas Slow rats showed levels similar to baseline values. Levels of noradrenaline and dopamine, but not of serotonin, were also increased in both strains throughout the MS treatment. In Fast rats, a dramatic lengthening of AD durations occurred 7 and 14 days following MS, as well as subsequent strong positive transfer to daily kindling, all of which were not seen in Slow rats. Together, these results show that repeated, closely spaced stimulations of the amygdala can differentially alter excitatory and/or inhibitory transmitter levels in a seizure network, and that sensitivity to this manipulation is genetically determined.

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Excitatory Amino Acid Receptors and Phosphoinositide Breakdown: Facts and Perspectives

Récasens

Mayat

Guiramand

1991

Current Aspects of the Neurosciences

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Changes in cortical amino acids during electrical kindling in rats

Cited by 39 publications

References 14 publications

Synthesis and Structure−Activity Relationships of 6,7-Benzomorphan Derivatives as Use-Dependent Sodium Channel Blockers for the Treatment of Stroke

Synthesis and Structure−Activity Relationships of 6,7-Benzomorphan Derivatives as Use-Dependent Sodium Channel Blockers for the Treatment of Stroke

Amygdala amino acid and monoamine levels in genetically Fast and Slow kindling rat strains during massed amygdala kindling: a microdialysis study

Excitatory Amino Acid Receptors and Phosphoinositide Breakdown: Facts and Perspectives

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