Cerebellar and striatal dopamine receptors: effects of reeler and weaver murine mutations.

The presence and the binding characteristics of D1 and D2 receptors were investigated in normal-reeler and normal-weaver mutant mice utilizing [3H]spiperone (D2 antagonist), [3H]SKF 38393 (D1 agonist), and [3H]DA as ligands. Analysis of the binding data showed that in the cerebellum there are two binding components for all [3H]ligands. Comparison of the binding constants from cerebellum and striatum showed that in cerebellum the high affinity-low capacity component has similar affinity with that of striatum. The reeler and weaver mutations affected the binding of all ligands: In reeler, total cerebellar specific binding sites for [3H]spiperone and [3H]SKF 38393 decrease significantly (approximately 50% and approximately 70%, respectively), while those for [3H]DA show a small (approximately 10-15%) but not significant decrease. In weaver, total cerebellar specific binding sites for [3H]spiperone, [3H]SKF 38393, and [3H]DA also decrease significantly (approximately 60%, approximately 70%, and approximately 50%, respectively). In reeler striatum [3H]SKF 38393 binding (Bmax) is significantly decreased (approximately 24%), while [3H]spiperone and [3H]DA binding (Bmax) is not affected. In weaver striatum, [3H]SKF 38393 binding is significantly increased (approximately 40%), while [3H]DA binding (Bmax) decreases significantly (approximately 70%). On the basis of the cytoarchitectural aberrations that characterize the cerebellum of these mutants and some well-established information regarding the dopaminergic system of the cerebellum, the above results indicate that in this region a) D1 receptors are mainly localized on granule cells and b) D2 receptors are localized postsynaptically on granule cells and presynaptically on the DA fibers innervating the cerebellum.