Differential pharmacological profile of striatal and cerebellar dopamine receptors labeled by [3H]quinpirole: identification of a discrete population of putative D3 receptors.

Abstract

We have previously identified [3H]quinpirole-labeled dopamine receptors in the molecular layer of cerebellar lobule 10 which have a D2-like pharmacological profile, are guanine nucleotide-insensitive, and are juxtaposed to putative D3 receptor mRNA. This study compares the pharmacological profiles of [3H]quinpirole-labeled dopamine receptors in striatum and cerebellar lobule 10 using quantitative autoradiography. Dopaminergic compounds inhibited the specific binding of [3H]quinpirole in the caudate/putamen with the following rank order of potencies: spiperone > haloperidol > or = (+)butaclamol > or = quinpirole > or = 7-OH-DPAT > or = bromocriptine > clozapine > (-)sulpiride. In cerebellar lobule 10, a somewhat different rank order of potencies was observed: 7-OH-DPAT > quinpirole > or = bromocriptine > spiperone > (+)butaclamol > haloperidol > clozapine > (-)sulpiride. Quinpirole possessed equal affinity for [3H]quinpirole-labeled receptors in the caudate/putamen and cerebellum. 7-OH-DPAT exhibited 5-fold greater affinity for cerebellar receptors than those in the caudate/putamen. Spiperone, haloperidol, (+)butaclamol, and clozapine were more potent in competing for [3H]quinpirole binding at striatal dopamine receptors than cerebellar receptors by 83-, 59-, 11-, and 6-fold, respectively. The relative potencies of these compounds at striatal and cerebellar dopamine receptors are generally similar to the differential affinities reported at D2 and D3 dopamine receptors expressed in CHO cells, respectively. These data provide additional evidence that the dopamine receptors observed in cerebellar lobule 10 represent a discrete population of putative D3 receptors.