Drug-induced rotation in rats without lesions: behavioral and neurochemical indices of a normal asymmetry in nigro-striatal function.

Normal unoperated rats were tested for rotation (i.e., circling behavior) in a spherical "rotometer" and dose-response relationships were generated using d-amphetamine, apomorphine, L-Dopa, haloperidol, and scopolamine. The rotation induced by amphetamine was significantly antagonized by alpha-methyl-p-tyrosine and haloperidol, but not by diethyldithiocarbamate. The rotation elicited by apomorphine was unaffected by alpha-methyl-p-tyrosine. Rotation was not necessarily in the same direction with high and low doses of amphetamine, or amphetamine and apomorphine administered a week apart from each other. Dopaminergic-cholinergic interactions were evident, since pilocarpine antagonized amphetamine-induced rotation whereas scopolamine did not; scopolamine elicited rotation in the same direction as that induced by amphetamine. Left and right striatal dopamine and tel-diencephalic norepinephrine levels were determined in rats injected with various doses of amphetamine and tested for rotation. There were significant bilateral differences in striatal dopamine which were related to the direction of rotation. Since amphetamine was found to be equally distributed to the two sides of the brain, the difference in striatal dopamine appeared to be the neurochemical substrate for rotation in normal rats. These results suggest that normal rats have asymmetrical levels of striatal dopamine as well as an asymmetrical complement of striatal dopamine receptors.