Drugs That Increase Γ‐aminobutyric Acid Transmission Protect Against the High Pressure Neurological Syndrome

Bichard, A.R.; Little, H.J.

doi:10.1111/j.1476-5381.1982.tb09238.x

Cited by 39 publications

(9 citation statements)

References 17 publications

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“…The h increased the marked differences in potency of these simple and that for con-isomers suggests that pressure may exert its action p83). This marked not by a general perturbation of the bulk properties s of HPNS is a of the lipid portion of the cell membrane, as has been ?NS properties of widely believed (Miller, 1985) (Brauer, 1975;) and alternative models to account for the sub- (Bichard & Little, 1982). However, the discovery that muscimol, a…”

Section: Resultsmentioning

confidence: 99%

“…GABAA-receptor agonist (Bichard & Little, 1984), and baclofen, a GABABreceptor agonist (BowserRiley, 1984), are ineffective against HPNS and that the convulsive action of picrotoxin is not additive with that of pressure, all suggest that GABA may not play a direct role in determining the response to pressure. The suggestion that pressure may bring about its effects by an intensification of excitatory mechanisms linked to the dicarboxylic acid transmitters, aspartate and glutamate, was proposed to explain the anti-HPNS actions of APH and PDA (cis-2,3-piperidine dicarboxylic acid) (Meldrum et al, 1983;Wardley-Smith & Meldrum, 1984).…”

Section: Resultsmentioning

confidence: 99%

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Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2‐propandiols in the mouse

Bowser-Riley¹,

Daniels²,

Smith³

1988

British J Pharmacology

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1 The effects of a variety of structural isomers of the centrally acting muscle relaxant mephenesin on the high pressure neurological syndrome have been investigated. Threshold pressures for the onset of the behavioural signs, tremors and convulsions, were established. The effects of these compounds on the response to pressure were also compared with their ability to antagonize the convulsive action of strychnine. 2 The dose-response relationships for strychnine and picrotoxin were investigated at fixed pressures. Additionally, the dose-response relationship of strychnine, in the presence of mephenesin, at pressure was investigated. 3 All the isomers of mephenesin protected against the effects of both pressure and strychnine. The relative potency was found to be identical with respect to both. Mephenesin was clearly the most effective; it raised the threshold pressure for tremors by 2.5 times, that for convulsions elicited by pressure by 1.5 and the ED30 for strychnine convulsions by 1.6 times. Strychnine was found to be strictly additive with pressure whereas picrotoxin exhibited gross deviations from additivity. Mephenesin ameliorated the combined effects of pressure and strychnine equally. 4 The marked dependence on structure of the anticonvulsant activity of the mephenesin isomers can be interpreted as evidence that pressure acts not by some general perturbation of the membranes of excitable cells but rather via some specific interaction. The finding that strychnine and pressure are strictly additive supports the idea of specificity and also indicates that they may share a common mechanism in the production of convulsions. By analogy with the established mechanism of action of strychnine, it is suggested that the hyperexcitability associated with pressure might arise from an action on glycine-mediated inhibitory processes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2‐propandiols in the mouse

Bowser-Riley¹,

Daniels²,

Smith³

1988

British J Pharmacology

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“…Behavioural signs in the rat include tremors, myoclonus and convulsions. The mechanism of the HPNS remains unknown but it has been suggested that increasing GABA transmission delays its onset (Bichard & Little, 1982). These authors found that sodium valproate and flurazepam were more effective than amino-oxyacetic acid and diaminobutyric acid.…”

Section: Pmentioning

confidence: 64%

Proceedings of the Physiological Society, 13‐14 January 1984, Mill Hill Meeting: Communications

1984

The Journal of Physiology

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Rana catesbiana tadpoles regeneration of long axon pathways does not occur before metamorphosis and that during metamorphosis only descending long axon pathways are regenerated (Forehand & Farel, 1982). In contrast, we can now report that in Rana temporaria tadpoles following cord transaction at least one ascending pathway, the sensory dorsal column, is regenerated and this can occur before metamorphosis is complete.The thoracic spinal cord was completely transacted in stage VII (Taylor & Kollros, 1946) tadpoles anaesthetized in MS 222. Animals were allowed to recover and kept for between 26 and 41 days in tanks of shallow aerated water. The projection of lumbar dorsal root fibres in operated and unoperated animals were analysed morphologically following HRP application to the dorsal roots or to the severed right sciatic nerve, or electrophysiologically by antidromic activation of dorsal root fibres by stimulation of the dorsal columns.In unoperated and in eight out of ten operated animals, antidromic action potentials in the lumbar dorsal roots were evoked by electrical stimulation of the dorsal medulla just rostral to the obex. The potentials recorded were compound action potentials whose individual components were of constant latency and shape at stimulus frequencies up to at least 50 Hz. The maximum amplitudes of these potentials were always less in operated than control animals. Four of the ten operated animals were tested before the emergence of the tadpoles' forelimbs (stage XX), the remaining six were tested after metamorphosis. One animal from each group showed no signs of dorsal column regeneration.In six unoperated animals most HRP-labelled dorsal column axons extended to a region in the dorsal medulla between the obex and the level of the Xth cranial root. A few fibres continued through the medulla and entered the cerebellum. The analysis of five operated HRP-labelled animals confirmed that many axons from lumbar dorsal roots had grown through the transaction site. In each case, axons could be followed beyond the obex but none further than the Xth cranial root. As in control animals, most of these axons fasciculated in a distinct dorso-medial tract through the brachial cord and caudal medulla, while a few fibres occupied more dorsolateral positions. Although we have clear evidence that the dorsal column pathway is regenerated, we cannot be sure that the axons that grow through the cut are those severed at the time of operation.

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“…In the anticonvulsant dose of 400 mg/kg (33–35), VPA did not alter slow‐wave activity in wild‐type mice (Fig. 4B), but in heterozygotes reduced EEG slowing in the first postinjection epoch (p = 0.011).…”

Section: Resultsmentioning

confidence: 96%

Pharmacologic Evidence for Abnormal Thalamocortical Functioning in GABA_A Receptor β3 Subunit–Deficient Mice, a Model of Angelman Syndrome

et al. 2005

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Summary:Purpose: γ -Aminobutyric acid receptor (GABA A r) subunit β3-deficient mice model Angelman syndrome by displaying impaired learning, abnormal EEG with interictal spikes and slowing, myoclonus, and convulsions. The β3-subunit deficiency causes a failure of intrathalamic reticular nucleus inhibition, leading to abnormally synchronized thalamocortical oscillations. We postulated that this pathophysiology underlies the abnormal cortical EEG and triggers interictal spikes and seizures, but extrathalamic regions also contribute to interictal spikes and seizures, so that the EEG slowing should reveal an absence-like response profile, whereas spikes and seizures have dual responsiveness to absence and partial-seizure drugs.Methods: Recording electrodes were implanted over the parietal cortices of wild-type, heterozygotes, and homozygous null mice. In each experiment, EEG was recorded for 45 min, either drug or vehicle administered, and EEG recorded for another 3 h. Each EEG was scored for slow-wave activity, interictal spikes, and seizures by a reader blinded to treatments. Results:Interictal spiking and percentage of time in EEG slowing in heterozygotes were increased by the proabsence drug baclofen (GABA B -receptor agonist), whereas CGP 35348 (GABA B -receptor antagonist) had the opposite effect. The antiabsence drug ethosuximide markedly suppressed EEG slowing and interictal spiking in heterozygote and null mice. Broadspectrum clonazepam and valproate were more effective on interictal spiking than on EEG slowing, and fosphenytoin suppressed only interictal spiking.Conclusions: The results suggest that this model of Angelman syndrome, although not expressing typical absence seizures, is characterized by hypersynchronous thalamocortical oscillations that possess absence-like pharmacologic responsiveness and promote EEG slowing, interictal spikes, and convulsive seizures.

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Drugs That Increase Γ‐aminobutyric Acid Transmission Protect Against the High Pressure Neurological Syndrome

Cited by 39 publications

References 17 publications

Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2‐propandiols in the mouse

Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2‐propandiols in the mouse

Proceedings of the Physiological Society, 13‐14 January 1984, Mill Hill Meeting: Communications

Pharmacologic Evidence for Abnormal Thalamocortical Functioning in GABA_A Receptor β3 Subunit–Deficient Mice, a Model of Angelman Syndrome

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Drugs That Increase Γ‐aminobutyric Acid Transmission Protect Against the High Pressure Neurological Syndrome

Cited by 39 publications

References 17 publications

Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2‐propandiols in the mouse

Investigations into the origin of the high pressure neurological syndrome: the interaction between pressure, strychnine and 1,2‐propandiols in the mouse

Proceedings of the Physiological Society, 13‐14 January 1984, Mill Hill Meeting: Communications

Pharmacologic Evidence for Abnormal Thalamocortical Functioning in GABAA Receptor β3 Subunit–Deficient Mice, a Model of Angelman Syndrome

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Pharmacologic Evidence for Abnormal Thalamocortical Functioning in GABA_A Receptor β3 Subunit–Deficient Mice, a Model of Angelman Syndrome