The aim of this study was to find a rapid and suitable method for testing the toxicity of drugs upon the vestibular end organs. The experiments were performed in the frog and the action of two antibiotics, streptomycin sulphate and penicillin G, was studied by carefully observing the equilibrium behaviour of the animals and recording the spontaneous activity of the nerve of the horizontal semicircular canal. The results obtained show that: 1) injection of streptomycin sulphate (20 microgram) directly into the labyrinthic cavity elicited disorders of the equilibrium and reduced the spontaneous activity of the horizontal canal nerve; 2) these disorders were reversible or not depending on the animal; 3) there is a good correlation between behavioral observations and electrophysiological data (i.e. the activity of the ampullary nerve was low in frogs whose behaviour was impaired at the time of sacrifice; the activity did not differ from controls when the normal behaviour was completely restored); 4) injection of penicillin G or 0.7% NaCl into the labyrinthic cavity had no effect on the equilibrium of the frogs or on the activity of the ampullary nerve; 5) intramuscular or intralymphatic injections of streptomycin sulphate produced a neuromuscular block but did not alter the activity of the ampullary nerve. In conclusion, the question of ototoxicity is discussed.

Action Potentials↗

PubMedDate not supplied

Are interrelations between vestibular receptors mediated by Scarpa's ganglion? An electrophysiological study in the frog.

In the frog we have recorded, in "isolated head" preparations, the gross activity and single afferent fibre discharges from the ampullary nerve of the vertical anterior semicircular canal (VAC) in several experimental situations. In all the preparations the efferent vestibular fibres acting on the VAC were functionally eliminated by acute section of the vestibular nerve between Scarpa's ganglion and the brain stem (CVNa preparations) or, by section of the anterior branch of the vestibular nerve between Scarpa's ganglion and the peripheral receptors, close to the ganglion (SGE preparations) or, by section of the VAC ampullary nerve near the ampulla (PE preparations). 1) In CVNa preparations, mechanical stimulation of the horizontal canal was carried out by pressure exerted upon the ampulla in such a way that the cupula was deflected towards the utricle which elicited a long-lasting discharge on the whole VAC nerve which was detached from its ampulla. 2) In SGE and PE preparations, the mean frequencies of the spontaneous discharges calculated on more than 200 VAC afferent fibres had the same value; they were significantly higher than the mean frequency calculated in CVNa preparations. These results confirm the existence of interrelations between the vestibular receptors of the frog by means of receptor-receptor fibres. They also strongly suggest that Scarpa's ganglion is required for their action.

Action Potentials↗

PubMedDate not supplied

Curare and the efferent vestibular system. An electrophysiological study in the frog.

In the frog we have studied the action of d-tubocurarine on the spontaneous discharge recorded from the whole horizontal semicircular canal (HC) nerve and from single HC afferent fibres. Gross activity was recorded in isolated head preparations. In each case, the spontaneous frequency was measured 6 min before and 16 min after a drop of D-tubocurarine (0.1 microliter, 5.10(-6)M) dissolved in Ringer or after a similar drop of Ringer was injected into the perilymph near the HC ampulla. Curare elicited a significant increase of the discharge frequency in about 60% of the preparations and a decrease in 6-8% of the cases, whether the contralateral eighth nerve was cut or not, while Ringer had no effect. After severing of the ipsilateral eighth nerve anterior branch, curare had no significant effect on the mean resting rate (calculated from 25 preparations), while in a few cases it evoked an increase or a decrease of the discharge frequency. Single afferent discharges were recorded in intact frogs. The mean frequency calculated from about 200 afferent fibres was 21.4 +/- 1.7 spikes/s after curare treatment, while it was only 15.6 +/- 1.3 spikes/s after Ringer injection; these two values are highly significantly different. From these results we conclude that the ampullary receptors are tonically subject to an inhibitory influence probably due to the tonic activity of the cholinergic efferent vestibular system. Moreover, the activity of the hair cells is probably also controlled by another, as yet unknown cholinergic mechanism.

Afferent Pathways↗

PubMedDate not supplied

Local mechanisms in vestibular receptor control. Effects of curare on the EPSPs and spike discharge recorded from single afferent fibres of the posterior canal nerve of the frog.

In the frog, the afferent discharge of EPSPs and spikes has been recorded intracellularly from single fibres of the posterior ampullar nerve before and after administration of D-tubocurarine (5 X 10(-6) M) in the following experimental conditions: (a) in animals in which the labyrinth was merely exposed (intact frogs), (b) in isolated acute labyrinth preparations, (c) in isolated chronic labyrinth preparations after degeneration of the efferent fibres. In both (a) and (c), curare induced either facilitation or inhibition of the resting discharge in a large number of units. By contrast, after degeneration of the efferent fibres, the effects of the drug were almost completely suppressed. These results indicate the existence of peripheral mechanisms involving the efferent nerve terminals which can control the release of afferent transmitter even in the absence of any central influence.

Animals↗

PubMedDate not supplied

Comparative vestibular toxicity of dibekacin, habekacin and cisplatin.

The vestibular toxicity of two aminoglycoside antibiotics, dibekacin sulfate and habekacin sulfate, and of a drug with potent antimitotic activity, cisplatin (cis-diamminedichloroplatinum) has been investigated in both rats and frogs. In rats, chronic intraperitoneal injection of a saline solution of dibekacin (50 mg/kg/day), habekacin (50 mg/kg/day), cisplatin (0.5 mg/kg/day) for 4 weeks and of cisplatin (1 mg/kg/day) for 5 weeks, produced no behavioral vestibular disorders and the righting reflex could be elicited at any time. In frogs, the spontaneous discharge was recorded from individual fibres of the ampullary nerve of the horizontal semicircular canal before and after acute administration of the drugs, dissolved in Ringer, into the perilymph of the inner ear near the horizontal ampulla. Following injection of 1 microliter of solutions containing 10 micrograms or 20 micrograms of dibekacin, 20 micrograms or 50 micrograms of habekacin, 0.5 micrograms, 2.5 micrograms or 10 micrograms of cisplatin, the spontaneous discharge decreased in a number of fibres and was sometimes completely abolished. The vestibular toxicity of the three drugs tested is discussed with respect to that of aminosides whose ototoxicity is well known.

Aminoglycosides↗

PubMedDate not supplied

[Functional relationships between the horizontal and vertical anterior semicircular canals in the labyrinth of the frog (Rana esculenta L.)].

We have studied the vestibular postrotatory reactions (reactions elicited by the stimulation of the horizontal semicircular canals) in the frog blinded by section of optic nerves, before and after section of the ampullary nerves of the vertical anterior semicircular canals (VAC). 90 frogs have been studied. In 30 frogs the ampullary nerves of the two VAC have been cut; in 60 animals either the ampullary nerve of the right VAC or of the left VAC has been cut. Both after section of the ampullary nerves of the two VAC and after section of the ampullary nerve of one VAC, the postrotatory reactions were decreased in about the half of the animals. The decrease of the postrotatory reactions is not due to a lesion of the ampullary nerves of the horizontal semicircular canals and it may be explained by the existence of functional connections between the VAC and the horizontal canal.

Animals↗