BEHAVIORAL AND NEUROCHEMICAL DATA SUGGEST FUNCTIONAL DIFFERENCES BETWEEN DOPAMINE D-2 AND D-3 RECEPTORS

In an in vitro model for mitogenic activity in cloned Chinese hamster ovary (CHO) cells expressing rat dopamine D-2 or D-3 receptors, the EC (50)D(2)/EC(50)D(3) ratios for the agonists, apomorphine, (+)-3-hydrox y-N-n-propyl-phenylpiperidine ((+)-3-PPP), quinpirole, R-(+)-7-hydroxy -2-(di-n-propylamino)tetralin (R-(+)-7-OH-DPAT) and pramipexole (SND91 9) were found to be 0.36, 0.41, 1.3, 3.7 and 7.0, respectively. In loc omotor activity experiments with actively exploring rats, the more dop amine D-3 preferring agonists, R-(+)-7-OH-DPAT and pramipexole, were m ost efficacious to reduce locomotion. The hypoactivity was also observ ed at doses that did not affect brain dopamine synthesis rate (DOPA ac cumulation) or release (measured in in vivo dialysis experiments). In contrast, for apomorphine, (+)3-PPP and quinpirole there was a closer correlation between doses that reduced exploratory activity and doses that reduced brain dopamine release and synthesis. The present data su pport the hypothesis that the functional dopamine D-3 receptor is a po stsynaptic receptor inhibitory on rat locomotion.