L-Dopa and dopaminergic agonists selective for the D1- or D2-dopamine receptor subtype induce contraversive rotation in rats which have been unilaterally lesioned with injections of 6-hydroxydopamine (6-OHDA) into the substantia nigra. D-Amphetamine, which releases dopamine from neurones on the unlesioned side of the animal, causes ipsiversive rotation. These increases in rotational behaviour are mediated, at least in part, by dopamine receptors in the striatum. In unilaterally lesioned animals, L-dopa and the D1-selective agonists SKF 38393 and CY 208-243 produce contralateral rotation and induction of the nuclear proto-oncogene c-fos in the lesioned striatum. D-Amphetamine induces both ipsilateral rotation and c-fos activation in the intact striatum. Three lines of evidence, however, dissociate fos induction and rotation. First, LY 171555, a selective D2-dopamine receptor agonist, also induces contraversive rotation but this rotation is not accompanied by c-fos activation in striatum. Second, D1-dopamine agonists produce activation of striatal c-fos even if rotation is prevented by an anaesthetic. Third, rotation induced by injection of SKF 38393 into substantia nigra is not accompanied by c-fos induction. These results suggest a mechanism by which D1-dopamine receptor mechanisms may regulate long-term changes in dopaminergic systems.
