DOPAMINE-RECEPTOR AGONIST POTENCIES FOR INHIBITION OF CELL FIRING CORRELATE WITH DOPAMINE D-3 RECEPTOR-BINDING AFFINITIES

The potencies for in vivo inhibition of substantia nigra pars compacta dopamine single cell firing were determined for apomorphine, BHT 920, N-0923, (+/-)-7-hydroxy-dipropylaminotetralin (7-OH-DPAT), (+)-3-(3-hydroxyphenyl)-N-propylpiperidine (3-PPP), pramipexole, quinelorane, quinpirole, RU 24926, U-86170, and U-91356. Significant correlation was obtained between the potencies of these 11 highly efficacious dopamine receptor agonists and the in vitro binding affinities at dopamine D-3 receptors, but not at dopamine D-2L receptors. These results support a functional role for the dopamine D-3 receptor subtype in the autoreceptor-mediated regulation of dopamine cell activity, while a role for dopamine D, receptors awaits further analysis. In addition, the results demonstrate the limitations of using currently available dopamine receptor agonists to delineate relative in vivo roles for the dopamine D-2 and D-3 receptor subtypes.