Brain neuronal RNA metabolism during sustained low-level soman toxication

Quantitative azure B-RNA cytophotometry was used to monitor metabolic responses of cholinergic elements of the rat brain during sustained low-level administration of soman (0.25-0.50 LD50, sc). RNA contents of caudate and cerebrocortical (Layers III and V) neurons were measured 60 min following 1-5 soman dosages given at 24 h intervals. Marked and progressive RNA depletion was evidenced after 1-4 soman injections, whereas partial or complete restitution of RNA levels was observed following the fifth injection. These data indicate that repetitive soman toxication is associated with metabolic correlates of impaired rather than accentuated activation of CNS cholinergic systems, and that tolerance is developed to CNS actions of the agent. It is postulated that impaired neuronal activation is related to soman or ACh-induced transmission block, and that the same adaptive processes responsible for recovery during acute poisoning may underlie the development of tolerance during repetitive administration of organophosphates.