Fish electroreception as a model for vincristine-induced neuropathies and a possible preventive role for Org 2766 treatment

Abstract

1. Subcutaneous injection of vincristine (more than 3 μg) in the catfish, Ictalurus nebulosus, produces a black spot on the skin with a grey surround. Doses between 1 and 3 μg give a less pronounced discolouration. 2. Two to three days after injection of 5 μg vincristine, repetitive activity is detected in primary afferents of unstimulated electroreceptor organs close to the site of injection. 3. Vincristine increases the phase-lag of the modulation of afferent activity in electroreceptor organs during electrical stimulation without a clear effect on the sensitivity of catfish electroreceptor organs. 4. The amplitude of the action potentials of the primary afferents begins to decrease after 2 days; after 3 days they gradually disappear in the background noise. 5. Application of Org 2766, a potentially neurotrophic compound, at 2 days, but not 1 day, before vincristine application prevents vincristine effects on the phase shift. 6. Preliminary electron-microscopical studies of the synapse shows a severe depletion of glycogen granules in the afferent nerve fibre after vincristine application, 7. It is concluded that electroreceptor organs can be used to study neuropathies caused by vincristine, and that Org 2766 may be useful for preventive treatment of such neuropathies.