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 (≈50% and ≈70%, respectively), while those for ³H]DA show a small (≈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 (≈60%, ≈70%, and ≈50%, respectively). In reeler striatum ³H]SKF 38393 binding (B_max) is significantly decreased (≈24%), while ³H]spiperone and ³H]DA binding (B_max) is not affected. In weaver striatum, ³H]SKF 38393 binding is significantly increases significantly (≈40%), while ³H]DA binding (B_max) decreases significantly (≈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. © 1993 Wiley-Liss, Inc.