Use of an experimental autoimmune model to define nerve growth factor dependency of peripheral and central substance P-containing neurons in the rat.

Rats exposed to maternal antibodies against nerve growth factor (NGF) in utero and in milk have been used to investigate the developmental dependency of various substance P-containing neurons on NGF. Substance P and other peptides were measured by radioimmunoassays. The substance P content of sensory ganglia, spinal cord, and skin was depleted 40 to 60% in anti-NGF-treated rats. These results demonstrate the NGF dependence of substance P-containing neurons in sensory ganglia. Opiate binding in the spinal cord was not changed despite the large depletion in substance P: the Bmax and KD were the same in control and treated animals. The results suggest that opiate receptors may not be located presynaptically on substance P-containing primary afferents. Among the peripheral tissues which were assayed (ileum, submaxillary gland, retina, and adrenal), substance P decreased only in the adrenal, suggesting innervation by a NGF-dependent substance P-containing neuron. No changes were detected in the substance P content of nine different brain regions, in agreement with previous observations on the lack of effect of NGF on central neurons.