Because of their purported specificity for the nervous system, the neurotoxic effects of triethyllead, trimethyllead, triethyltin, and trimethyltin were studied in rats. Initial experiments found that these metals produced dose- and time-related antinociception. Subsequent studies found that triethyl and trimethyl lead produce behavioral effects that are similar, but not identical. Histological assessment of rats 7 or 28 days after a single injection of these agents indicated that triethyllead caused structural abnormalities in the hippocampus and dorsal root ganglion, while trimethyl lead produced changes primarily in the spinal cord and brainstem. Comparison of the neurochemical effects of these four alkylmetals indicated that triethyltin, triethyllead and trimethyllead produce somewhat nonspecific changes in regional brain levels of biogenic amines and amino acid transmitters. However, trimethyltin produced relatively specific decreases in inhibitory transmitters in the hippocampus and frontal cortex. Because of its environmental relevance, further studies characterized the effects of triethyllead. These experiments found that the antinociception produced by this metal is probably not associated with an alteration in opiate systems. Subsequent experiments suggested that acute exposure to triethyllead enhances the responsiveness of dopaminergic processes which contribute to locomoter activity; selective depletion of brain dopamine with 6-hydroxydopamine was found to block the antinociceptive effects of triethyllead. Acute and short-term repeated exposure to triethyl alters reactivity, locomotor activity and avoidance learning. Other experiments indicated that triethyllead-induced behavioral changes may be related to alterations in reactivity to stress and damage to the hippocampus. However, other studies found that triethyllead had no significant effect on spatial learning in rats, indicating a lack of specificity for the limbic system. No further work in this area is planned.
