Quantitative autoradiography of Gpp(NH)p sensitive and insensitive [3H]quinpirole binding sites in the rat brain

Recent advances in the cloning of dopamine receptor subtypes have resulted in the detection of at least 5 genetically distinct subtypes of the dopamine receptor. The dopaminergic agonist, quinpirole, has relatively high affinity for the cloned D-2, D-3, and D-4 receptor subtypes. The D-3 receptor is unique within these 3 subtypes in that it does not appear to have sensitivity to guanine nucleotides. In order to localize the brain regions containing these subtypes of the dopamine receptor, the distribution of [3H]quinpirole binding sites in the rat brain was mapped by autoradiography. Labelling in the absence and presence of the nonhydrolyzable GTP analog, guanylyl-5'-imidodiphosphate (Gpp(NH)p) allowed differentiation between the high affinity agonist conformation of the D-2 receptor and the D-3 receptor. The highest densities of [3H]quinpirole binding were found in the caudate-putamen, nucleus accumbens, islands of Calleja, and olfactory tubercle which is consistent with the distribution of dopamine receptors seen with "classical D-2" receptor agonist and antagonist radioligands. In the presence of 10 microM Gpp(NH)p, binding was reduced in all these areas with the exception of the islands of Calleja. Additional areas which exhibited no change in binding when incubated with Gpp(NH)p included the nodulus and flocculus of the cerebellum. Several areas exhibited a partial reduction in binding including the glomerular layer of the olfactory bulb, nucleus accumbens, and the superior colliculus. The distribution of these subtypes is consistent with the distribution of mRNA for the D-2 and D-3 receptor in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)