Cobalt injections into the substantia nigra of the rat: effects on behavior and dopamine metabolism in the striatum

Small amounts of cobalt unilaterally injected into the substantia nigra of rats caused a strong, spontaneous contralateral turning which was suppressed by haloperidol. One to 2 days after intranigral cobalt microinjection, d-amphetamine decreased the intensity of the contralateral turning; 5 days after cobalt application, d-amphetamine changed the direction of the turning to the ipsilateral side. Intranigral cobalt microinjection initially caused a significant increase in the concentration of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the ipsilateral striatum. Thereafter, dopamine and its metabolites declined progressively to values significantly below control values. Similar biochemical changes in the striatum were also seen after partial electrolytic lesions of the substantia nigra. However, such lesions produced only mild contralateral turning. Frontal hemisection did not result in any increase of striatal metabolite values, and produced mild ipsilateral turning. Thus, there was no parallelism between the intensity and time course of the turning behavior induced by the different techniques and the changes in dopamine metabolism in the striatum. Within the cobalt-injected substantia nigra, γ-aminobutyric acid (GABA) and glutamic acid decarboxylase were decreased to less than 60% of the contralateral control values. The possibility is considered that the depression of a GABA-mediated inhibitory influence on the nigrostriatal or mesolimbic dopamine neurons may play a role in the cobalt-induced contralateral turning and altered striatal dopamine metabolism.