Toxin-induced inhibition of nerve terminal growth.

An in vivo model to permit the quantitative study of the effects of neurotoxins upon nerve terminal growth has been developed and used in practice to test the ability of methyl mercury chloride, leptophos, ethanol, morphine and acrylamide to inhibit nerve terminal growth. The model utilized the sympathetic innervation of rat submaxillary salivary glands. Nerve terminal growth was induced following crush of the sympathetic axons which innervated the submaxillary gland and quantified by measuring the return towards normal values of the density of sympathetic innervation in denervated glands. The nerve crush reduced the density of sympathetic innervation to a very low value but nerve growth began within 9 days and was sufficient to restore the density of innervation to approximately 70% of normal values in three weeks. Restoration of the original density of innervation took between 40 and 60 days. The major advantage of the model is its ability to detect and quantify 30% - 100% inhibition of nerve terminal growth. The major disadvantage is the time required to measure the density of sympathetic innervation though this can be minimized in a number of ways which are discussed. Acrylamide inhibited sympathetic nerve terminal growth without causing degeneration of sympathetic neurones. This demonstrates that toxins can selectively inhibit nerve terminal growth which will result in altered neuronal circuitry and abnormal function. Methyl mercury chloride, leptophos, ethanol and morphine did not inhibit sympathetic nerve terminal growth.