Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular target of streptomycin (STP) was investigated by analyzing the activity of glutamate decarboxylase (GAD) or choline acetyltransferase (ChAT) enzymes of synthesis of GABA and acetylcholine (Ach), respectively, [supposedly located in hair cells (GAD) or efferent terminals (ChAT)] in control and in 50 day-STP-treated colored guinea pig vestibular homogenates. Vestibular and auditory function were assessed by measuring postrotatory nystagmus response (PNR) and auditory brainstem evoked potentials (ABP). Morphological changes were followed by light and electron microscopy. STP-treated animals exhibited a GAD decrease of 83.6% with respect to controls whereas ChAT did not suffer any change. Assessment of PNR and ABP showed that STP affected only the former since animals lost it between the 20th and the 30th day of treatment, whereas ABP was not modified. Morphological experiments detected vestibular hair cell deterioration as the only cell type affected by STP. These results confirm the predilection of STP to affect vestibular function by damage to hair cells and show that this effect can be followed by measurement of GAD and ChAT in the vestibule as markers for hair cells and efferent terminals, respectively.
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PMID:Cellular target of streptomycin in the internal ear. 278 52

Guided and reflex eye movements were studied in cats trained to make orienting saccades toward visual and auditory targets. Injections of a GABA-agonist (Muscimol) or GABA-antagonists (Bicuculline and Picrotoxin) were made in the Substantia Nigra pars reticulata (SNpr). Bicuculline and Picrotoxin, whether unilaterally or bilaterally injected had no effect on the posture nor the oculomotor performance of the animals. Neck muscle activity remained symmetrical. Unilateral injections of Muscimol produced oro-facial akinesia, reduction of the number of eye movements, contralateral head turning, visual neglect mostly (but not only) for ipsilateral visual space. Balance between the gains of the vestibulo-ocular reflex (VOR) in the two directions of movement was changed. Gain was decreased for the ipsilateral rotation. The optokinetic nystagmus (OKN) was not affected. Contralateral neck muscles were hypertonic. After bilateral injections of Muscimol, the cats did not orient. The VOR was normal when the injections induced no postural asymmetry. Hypertony was bilateral. Implications of these results for the role of the basal ganglia in motor control are discussed. We suggest that in Parkinson's disease the fixed inhibitory drive of the SNpr on the tectum and on the thalamus is disrupted.
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PMID:Role of the cat substantia nigra pars reticulata in eye and head movements. II. Effects of local pharmacological injections. 298 33

This paper describes the EEG profiles, observed in rabbits, of drugs which affect GABA synaptic activity at GBB complex. Drugs which enhance GABA synaptic activity induce sedation associated with EEG synchronization. However, muscimol, THIP, GHB and baclofen induce signs of CNS stimulation (light tremors of the forelimbs, chewing, light nystagmus and hyperpnea) associated with EEG spikes. Signs of light stimulation (chewing and jerks of the head) also occur after BDZs and barbiturates, and are associated with the presence of 12-24 and 20-25 Hz waves, respectively. Drugs which reduce GABA synaptic activity (bicuculline, inverse BDZ agonists, PTZ, picrotoxin and Ro 5-3663) induce three dose-dependent stages of EEG changes: trains of slow waves, trains of spike-and-wave complexes and paroxysmal activity in the rostral encephalic structures without apparent changes of the electrical activity in the spinal cord. The first two stages are associated with a behavioral state of alert and the third stage with tonico-clonic convulsions. Among the inverse BDZ agonists, DMCM and beta-CCM elicit all three stages, whereas FG 7142 and beta-CCE induce only the first two and CGS 8216 only the first. The BDZ antagonists Ro 15-1788 and Ro 15-3505 (0.2-30 mg/kg IV) do not significantly affect the EEG pattern. However, they selectively inhibit the effects of diazepam and of the inverse BDZ agonists. In both cases, the inhibition is observed with doses as low as 0.2 mg/kg IV and leads to an EEG desynchronization. The possible involvement of the modifications of GABA synaptic activity in the etiology of both petit mal and grand mal epilepsies is discussed.
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PMID:Electroencephalographic investigations in rabbits of drugs acting at GABA-benzodiazepine-barbiturate/picrotoxin receptors complex. 299 34

1. Eye movements were observed following an injection of picrotoxin, a GABA antagonist, into the vitreous of one eye. A spontaneous nystagmus was observed in cats, rabbits, and turtles, even in total darkness, with slow-phase eye movements in the temporal-to-nasal direction for the injected eye. 2. During visual stimulation by a horizontal drifting pattern, injected eyes moved in the temporal-to-nasal direction, irrespective of stimulus direction. In cats, however, the nystagmus was usually slower when the injected eye viewed nasal-to-temporal motion (opposite to the direction of the spontaneous nystagmus). The spontaneous nystagmus could be halted or even reversed by allowing cats to view motion opposite to the direction of the nystagmus with the uninjected eye alone. The nystagmus could not be overridden in this fashion in rabbits or turtles. 3. The nystagmus induced by picrotoxin could also be modified by vestibular stimulation. When cats were placed on their sides, the spontaneous horizontal nystagmus often decreased and spontaneous vertical nystagmus with upward slow phase movements occurred. During sinusoidal horizontal vestibular stimulation, the horizontal nystagmus due to picrotoxin added to the vestibuloocular reflex as a velocity offset in the temporal-to-nasal direction. 4. Following bilateral ablation of the cat visual cortex, picrotoxin's effect became even more pronounced than before the ablation. Therefore, at least some picrotoxin-sensitive cells can use subcortical pathways, perhaps to the accessory optic nuclei. The visual cortex, which also processes directional information, may be able to compensate for changes in retinal processing induced by picrotoxin in intact animals. 5. This study demonstrates the importance of retinal GABA in the control of eye stability. As GABA is known to be responsible for null direction inhibition of directionally sensitive retinal ganglion cells, these results suggest that the output of these cells may be critical for the normal functioning of central optokinetic pathways, even in the absence of visual cortex.
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PMID:Analysis of vertebrate eye movements following intravitreal drug injections. II. Spontaneous nystagmus induced by picrotoxin is mediated subcortically. 317 54

1. Baclofen had a characteristic effect on vestibular and optokinetic nystagmus in rhesus monkeys. Each aspect of nystagmus that is dependent on the velocity-storage mechanism in the vestibulo-ocular reflex (v.o.r.) was altered by the drug: (a) Baclofen reduced the dominant time constant of the v.o.r. in a dose-dependent manner up to 5 mg/kg, the highest dosage used. The alteration in v.o.r. time constant began within 15 min of injection, was maximal between 1 and 4 h, and lasted for 14-18 h. This effect mirrors changes in plasma levels of baclofen after oral doses in humans (Faigle, Keberle & Agen, 1980). (b) Slow-phase velocities of steady-state nystagmus induced by rotation about axes tilted from the vertical (off-vertical axis rotation, o.v.a.r.) were reduced after baclofen and could not be maintained at previous levels. (c) There was a dose-dependent decline in the steady-state gain of optokinetic nystagmus (o.k.n.), and at the highest dosages little o.k.n. was induced. In parallel, the peak velocity and falling time constant of optokinetic after-nystagmus (o.k.a.n.) were reduced. Since baclofen is a GABA agonist, systems utilizing GABA and acting on GABAB receptors appear to produce inhibitory control of velocity storage. 2. The step gain of the v.o.r., measured at the beginning and end of constant-velocity rotation in darkness, was unaffected by baclofen, as were saccades, quick phases of nystagmus, and the ability to hold positions of fixation or to generate linear slow phases of nystagmus. This indicates that it is possible to use baclofen to manipulate the dominant time constant of the v.o.r. and of o.k.a.n. in relative isolation from effects on other oculomotor components. 3. Baclofen caused a dose-dependent reduction in the initial jump in eye velocity at the onset of o.k.n., suggesting that the initial jump is also under inhibitory control of GABAB receptors. However, there were still occasional slow phases with velocities up to 30-40 deg/s after baclofen, and animals were capable of visually suppressing the v.o.r. This indicates that pathways responsible for causing rapid changes in slowphase velocity were capable of functioning, at least intermittently, in the presence of the drug.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Baclofen and velocity storage: a model of the effects of the drug on the vestibulo-ocular reflex in the rhesus monkey. 344 8

In a monocular situation, an intravitreal injection of the GABA antagonists, bicuculline or SR 95103 provoked both the suppression of the optokinetic nystagmus (OKN) related to the injected eye and the appearance of a Nasal-Temporal (N-T) component in the OKN triggered by the contralateral non-injected eye (this N-T component being absent in control OKN). These two effects were added in a binocular condition. Similar results were obtained with L-C allylglycine which reduces the endogenous GABA level, but these effects were delayed when compared to those of GABA antagonists. All these data are roughly analogous to those previously obtained with picrotoxin (a non-competitive GABA antagonist) and thus confirm that GABA mechanisms are involved in the control of the frog OKN. Furthermore, SR 95103 acted in this model as a potent selective GABA antagonist, as has been demonstrated in another system.
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PMID:On GABAergic mechanisms in the optokinetic nystagmus of the frog: effects of bicuculline, allylglycine and SR 95103, a new GABA antagonist. 387 94

Frog optokinetic nystagmus (OKN) was studied before and after an intravitreal injection of picrotoxin, a specific non-competitive GABA antagonist. In monocular vision, the OKN displayed a directional asymmetry favouring the Temporal-Nasal (T-N) stimulation. In that case, the nystagmus extinction frequency (NEF) is low, about 2 frames/s. In binocular vision, the OKN is symmetrical with a facilitation of performances compared to monocular vision (NEF = 3 frames/s). In monocular as in binocular vision, an intravitreal injection of picrotoxin (between 1 X 10(-4) and 5 X 10(-3) M) provoked the disappearance of the injected eye OKN and a spectacular facilitation in the performances of the intact eye, with the appearance of a N-T component and the increase of the NEF value reaching 7 or 11.5 frames/s according to the experimental conditions. This contralateral facilitation was no longer observed after the optic nerve of the injected eye had been cut, indicating that such a facilitation can only be explained by alterations of a central process triggered by the visual input. It is concluded that GABAergic mechanisms might be responsible for the inhibition of the N-T component in the frog OKN and might be involved in the control of the power of temporal resolution in this animal.
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PMID:Involvement of GABAergic mechanisms in the optokinetic nystagmus of the frog. 660 72

Hydrocarbon solvents, xylene, styrene, methylchloroform, and trichlorethylene, given intravenously to rabbits produce a positional nystagmus. Due to their additional influence on rotatory nystagmus, one may conclude that their mode of action takes place in the central nervous system. Optokinetic (OKN) responses in rabbits, cats, and humans were also influenced by styrene. OKN responses have not yet been tested for the other solvents. A comparison is made with the effects of alpha-chloralose and the GABA-antagonists bicuculline and picrotoxin which produced similar disturbances. The GABA agonist, baclofen, prevents positional induced styrene nystagmus. It seems likely therefore that the solvents may act by blocking the cerebellar inhibition of vestibulo-oculomotor reflexes. Solvents given simultaneously in some combinations are either additive or synergistic in effect. The implications of these results for occupational medicine are self-evident.
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PMID:Vestibular and oculomotor disturbances caused by industrial solvents. 696 32

There is evidence that GABA acts as the excitatory neurotransmitter at synapses between vestibular hair cells and the afferent fibres in the mammalian labyrinth. The question arose as to whether certain vestibular dysfunctions such as labyrinthine vertigo could be treated in patients by influencing the peripheral GABA system by means of the GABA antagonist picrotoxin, a well known analeptic drug. With the application of slow infusion rates of only milligrams of picrotoxin a distinct suppression of peripheral spontaneous nystagmus, caloric excitability of labyrinths, and labyrinthine vertigo, without general CNS-induced arousal effect, was observed. A latent central spontaneous nystagmus can become manifest, whereas a manifest central spontaneous nystagmus remains unchanged. A future application of picrotoxin as a diagnostic and therapeutic tool in cases involving vestibular disorders is discussed.
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PMID:Suppressive action of picrotoxin, a GABA antagonist, on labyrinthine spontaneous nystagmus and vertigo in man. 706 10

Both the nucleus of the optic tract (NOT) and the superior colliculus (SC) are thought to play important roles in the regulation of eye movements. The superior colliculus contributes to visual orientation and saccades, and the nucleus of the optic tract contributes to the detection of slow movements of the visual surround. Recently, a GABAergic projection has been described between these two nuclei in the cat, a species with frontal vision. The present study aimed at determining whether a similar GABAergic pathway exists in the rabbit, a species with lateral vision. To study this pathway we used the retrograde tracer cholera-toxin (CTB) to identify NOT neurons projecting to the SC and GABA-antibody immunostaining to identify GABA-containing neurons and processes. CTB injections into the superficial laminae of the SC showed that GABAergic and non-GABAergic neurons in the NOT project to the SC. Both types of neurons have structural characteristics similar to other projection neurons in the NOT. In contrast to the NOT neurons projecting to the inferior olive (IO) which are mainly located in the rostral NOT, the GABAergic and non-GABAergic NOT-SC neurons are situated throughout the nucleus. The somata and principal dendrites of both neuron types receive numerous synaptic contacts from GABAergic terminals and only a few from retinals. The NOT projection neurons to the SC thus establish prominent excitatory and inhibitory links between the two structures, suggesting the existence of separate circuits that could interact through a GABAergic and non-GABAergic NOT-SC projection. It is further suggested that these circuits may be involved in the regulation of saccades in the SC during optokinetic nystagmus.
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PMID:GABAergic and non-GABAergic neurons in the nucleus of the optic tract project to the superior colliculus: an ultrastructural retrograde tracer and immunocytochemical study in the rabbit. 789 Aug 35


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