Functional and neurochemical correlates of potentiation of striatal asymmetry by callosal section

Abstract

AFTER lesions have been made in one side of the nigro-striatal system, rats have been found to rotate when administered drugs which release dopamine (such as amphetamines) or activate dopamine receptors (such as apomorphine) in the corpus striatum (see for example refs 1 and 2). Because this circling effect is specific to the nigro-striatal system³ and because it has been established that rats consistently rotate contralateral to the more active striatum (for example ref. 4), the lesion–rotation paradigm is now commonly used as a model for the study of nigro-striatal function. Studies^5,6 in our laboratory have shown that rats without lesions also rotate when administered doses of the same drugs larger than those administered to lesioned rats. As in lesioned rats, the directoin of rotation is consistent for normal rats; when tested on several different occasions with the same dose of the same drug, some rats consistently rotate to the right and others rotate to the left. This suggested that normal rats have an intrinsic asymmetry between left and right sides of the nigro-striatal system which is accentuated by drugs. This functional asymmetry corresponds to a chemical asymmetry⁷: the dopamine contents of normal left and right striata were found to differ by 10–15%. After administration of (+)-amphetamine, the dopamine contents of left and right striata were found to differ by 25%. Moreover, in response to (+)-amphetamine, rats consistently rotated contralateral to the side containing the most dopamine. This normal asymmetry suggests an inter-hemispheric mechanism that maintains or regulates the asymmetry. Mensah and Deadwyler⁸ demonstrated in rats a pathway between left and right caudate nuclei coursing through the ventral corpus callosum. It seemed plausible that this pathway may be part of the mechanism maintaining striatal asymmetry. We have now found that the striatal asymmetry is potentiated, both functionally and chemically, by callosal section.