Quantitative autoradiographic mapping of rat brain dopamine D3 binding with [I-125]7-OH-PIPAT: Evidence for the presence of D3 receptors on dopaminergic and nondopaminergic cell bodies and terminals

The regional distribution and cellular localization of dopamine D3 receptor s in the rat brain was examined using quantitative autoradiography. [I-125] 7-OH-PIPAT bound in a saturable and reversible manner and exhibited subnano molar affinity for a single population of GTP-insensitive sites. The pharma cological profile was characteristic of cloned D3 receptors and nonspecific binding was uniformly low. The highest levels of D3 receptors were measure d in the islands of Calleja, nucleus accumbens, ventral pallidum, substanti a nigra, and lobules 9 and 10 of the cerebellum. The high specific activity of this ligand also allowed detection of D3 receptors in other regions, in cluding the serotonergic dorsal and median raphe nuclei, indicating that th e distribution of this receptor is more widespread than previously apprecia ted. The cellular localization of D3 receptors in regions containing dopami nergic cells and terminals was examined by discrete injection of neurotoxin s. Lesion of dopaminergic neurons with 6-hydroxydopamine produced 50% decre ases in [I-125]7-OH-PIPAT binding in the nucleus accumbens and substantia n igra. Quinolinic acid lesion of neurons originating in the nucleus accumben s also produced approximately 50% decreases in D3 receptors in the nucleus accumbens, substantia nigra, and ventral pallidum. 5,7-Dihydroxytryptamine lesion of serotonergic cells and processes produced no changes in [I-125]7- OH-PIPAT binding. These results demonstrate the presence of D3 receptors in several brain regions not previously identified and suggest that D3 recept ors are expressed at somatodendritic and terminal levels of both dopaminerg ic and nondopaminergic cells within the mesolimbic dopamine system.