Substantia nigra and pentylenetetrazol threshold in rats: correlation with striatal dopamine metabolism.

The time course of the metrazol threshold in rats with electrolytic lesions of the substantia nigra presents variations inversely proportional to the changes in dopamine and its metabolites in the neostriatum. Thus initially dopamine is increased and the threshold lowered, then a progressive decrease in dopamine and its metabolite is accompanied by a progressive increase in metrazol threshold. This supports the hypothesis that changes in functional activity of the caudate nucleus are reflected in variations of the brain's susceptibility to generalized seizures. When cobalt chloride was injected into the substantia nigra there were biochemical changes in the neostriatum similar to those observed with electrolytic lesions, but the pentylenetetrazol threshold steadily decreased. This is probably due to the fact that cobalt induces a lesion which changes in extent with time to involve adjacent brain stem nuclei sensitive to its epileptogenic action.