STABILITY OF SYNAPTOSOMAL GABA LEVELS AND THEIR USE IN DETERMINING THE <i>IN VIVO</i> EFFECTS OF DRUGS: CONVULSANT AGENTS

Wood, J. D.; Russell, M P; Kurylo, E.; Newstead, J. D.

doi:10.1111/j.1471-4159.1979.tb11706.x

Cited by 83 publications

(35 citation statements)

References 21 publications

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“…1 could be used as a model to monitor drug-induced changes in GABA levels of nerve endings in the intact animal. Conspicuously, the finding that GABA levels increase during synaptosome preparation from rat brain regions without inclusion of 3-MP is in contrast with previous experiments by Wood et al (1979) using whole brains of mice for isolation of synaptosomes. In fact, these authors concluded from their experiments that GABA was not being metabolized during synaptosome preparation.…”

Section: Discussioncontrasting

confidence: 82%

“…Both drugs were studied in doses and times of administration previously found to result in about the same anticonvulsant effect against electroconvulsions in mice (LSscher, 1980). Although data obtained after subcellular fractionation may not accurately reflect the situation in the intact animal, previous studies with synaptosomes isolated from the whole brain of mice have indicated that valid information about in vivo alterations in nerve ending GABA levels can be obtained provided the data are analyzed carefully with respect to the possible occurrence of changes taking place during dissection, homogenization and fractionation of the tissue (cf., Wood et al, 1979;L~scher, 1981 a). Various control experiments in this respect have been carried out also for the synaptosomal model used in the present study.…”

Section: Discussionmentioning

confidence: 96%

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In vivo effects of anticonvulsant drugs on nerve terminal (synaptosomal) GABA levels in 11 brain regions of the rat

Löscher

Vetter

Böhme

et al. 1985

J. Neural Transmission

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The in vivo effects of two GABA-elevating drugs with anticonvulsant properties, namely valproic acid (VPA) and aminooxyacetic acid (AOAA), on nerve terminal GABA levels in discrete rat brain regions were studied by means of a newly developed synaptosomal model. The profile of synaptosomal GABA increases obtained with AOAA was quite different from that seen with VPA. Thus, AOAA (30 mg/kg i.p., 2 hours) caused significant increases in olfactory bulb, cortex, hippocampus, thalamus and cerebellum, whereas VPA (200 mg/kg i.p., 0.5 hour) significantly increased GABA also in hypothalamus, substantia nigra and superior and inferior colliculus. In contrast to the regional selectivity of both drugs with respect to synaptosomal GABA levels, AOAA in most regions was more potent than VPA in increasing whole tissue GABA levels determined prior to subcellular fractionation. The data thus demonstrate that comparison of GABA levels in synaptosomal fractions rather than homogenates from discrete brain areas provides a more sensitive index of the action of GABA-elevating drugs administered in vivo.

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Section: Discussioncontrasting

confidence: 82%

Section: Discussionmentioning

confidence: 96%

In vivo effects of anticonvulsant drugs on nerve terminal (synaptosomal) GABA levels in 11 brain regions of the rat

Löscher

Vetter

Böhme

et al. 1985

J. Neural Transmission

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“…For interpretation of low CSF GABA levels in patients with epilepsy, recent experimental studies in dogs are of interest, which suggested that CSF GABA reflects turnover and release of GABA rather than its steady-state concentration in the brain (Loscher, 1982a). In fact, in many pharmacologically induced seizure states it is not the overall brain GABA level that is critical, but rather the relative availability of newly synthesized GABA (Wood et al, 1979b). In line with these considerations, the level of GABA in CSF of dogs was found to be positively correlated with the seizure threshold of the animals, i.e., dogs with low CSF GABA level had a high seizure excitability and vice versa (Loscher, 19826).…”

Section: Discussionmentioning

confidence: 97%

Cerebrospinal Fluid γ‐Aminobutyric Acid Levels in Children with Different Types of Epilepsy: Effect of Anticonvulsant Treatment

Löscher

Siemes²

1985

Epilepsia

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The mean gamma-aminobutyric acid (GABA) level in lumbar CSF of 31 children with epilepsy was not significantly different from that of 41 age-matched controls. However, when the epileptic children were subdivided into untreated patients and patients treated with antiepileptic drugs, the medication-free subgroup had a significantly lower mean CSF GABA level than nonepileptic children. Patients controlled by anticonvulsant therapy had significantly higher CSF GABA levels than untreated epileptic patients. A more detailed analysis of the children taking antiepileptic medication indicated that the only drug that significantly increased GABA in CSF was valproic acid. Analysis of CSF data with respect to the seizure type of the patients showed that, compared with controls, significantly reduced average GABA levels were present in children with infantile spasms (mostly untreated) and unmedicated generalized tonic-clonic seizures, whereas treated children with generalized tonic-clonic seizures and patients with partial epilepsy (mostly treated) did not significantly differ from controls. The data provide further evidence that impairment of the central GABA system may be involved in human epilepsy.

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“…The decrease of GABA-ergic axon terminals at sites of experimental epileptic foci [9] and the induction of grand mal seizures after the experimental reduction of GABA levels in the brain [12] provide evidence in support of this role. Moreover, the GABA content of the CSF of epileptic patients was found to be low [11].…”

Section: Discussionmentioning

confidence: 98%

Prolactin levels in febrile and afebrile seizures

et al. 1995

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Transient hyperprolactinaemia has been reported to follow unprovoked seizures, a finding proposed to be useful in the differential diagnosis of epilepsy. There is also evidence that patients with unprovoked seizures may have high baseline prolactin levels, which could be of value in detecting those predisposed to epilepsy after a first convulsive attack. The purpose of this study was to examine whether prolactin levels are elevated: (1) postictally in febrile seizures and (2) interictally in afebrile seizures. In 17 children with simple febrile seizures, mean postictal prolactin value (370 +/- 160 mU/l, mean +/- SD) was significantly higher (approximately 0.001) than the mean baseline value of 18 seizure-free controls (202 +/- 136 mU/l). The mean baseline prolactin values were not significantly different: (1) in ten children with afebrile versus ten seizure-free controls and (2) in 18 children with febrile seizures associated with high risk for subsequent afebrile seizures versus 23 children with febrile seizures but unlikely to suffer from afebrile seizures. CONCLUSION. Postictal prolactin levels may be a useful marker of recent febrile seizures, while baseline prolactin levels do not appear to have any prognostic significance in afebrile seizures.

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STABILITY OF SYNAPTOSOMAL GABA LEVELS AND THEIR USE IN DETERMINING THE IN VIVO EFFECTS OF DRUGS: CONVULSANT AGENTS

Cited by 83 publications

References 21 publications

In vivo effects of anticonvulsant drugs on nerve terminal (synaptosomal) GABA levels in 11 brain regions of the rat

In vivo effects of anticonvulsant drugs on nerve terminal (synaptosomal) GABA levels in 11 brain regions of the rat

Cerebrospinal Fluid γ‐Aminobutyric Acid Levels in Children with Different Types of Epilepsy: Effect of Anticonvulsant Treatment

Prolactin levels in febrile and afebrile seizures

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