Rotational bias in intact rats following intrastriatal injections of dopaminergic drugs.

摘要

Following unilateral 6-OHDA lesions of the striatum, systemic dopamine agonists produce rotation due to receptor supersensitivity. Rotation following intrastriatal dopamine agonists in intact rats also has been reported, although these studies are few and contradictory. Dorsal striatal injection (0.5 microl) of the direct dopamine agonist apomorphine failed to caused rotation. In addition, neither the D1 agonist SKF 81297, the cAMP analogue Sp-cAMPS, nor the D2 agonist quinpirole affected rotation. In contrast, the dopamine releaser amphetamine (1.1, 10.9, 108.7 mM) caused significant contralateral rotation. This effect was reversed by coinjection of the D1 antagonist SCH 23390 (3.1 mM) but not by the D2 antagonist eticlopride. Rotation was also reversed by TTX coinjections (100 microM) but not by the NMDA antagonist AP7 or the kainate/AMPA antagonist CNQX. Thus, direct dopamine agonists in the striatum failed to cause behavioral asymmetry, whereas amphetamine induced contralateral rotation. This effect is mediated primarily by D1 receptors and requires concurrent neuronal activation that appears to be independent of glutamate receptor stimulation. These results are consistent with studies of Fos induction in normosensitive animals following dopamine agonists and are discussed in terms of changes in basal ganglia output pathway activity.