Quantitative autoradiography of [3H]piquindone binding sites (dopamine D2 receptors) in rat brain

(-)Piquindone is a new antipsychotic pyrroloisoquinoline derivative that binds to dopamine D2 receptors. We used in vitro quantitative autoradiography to determine the distribution of [3H](-)piquindone binding sites in rat forebrain. [3H](-)Piquindone binding to brain slices was sodium dependent, saturable and of high affinity (Kd = 5 nM at 0 degree C). In autoradiographic experiments, there was a good signal to noise ratio for [3H](-)piquindone binding with nonspecific binding representing only about 20% of total binding in caudate putamen. The D2 antagonists (-)sulpiride and raclopride were much more potent inhibitors of [3H](-)piquindone binding than the D1 antagonist SCH 23390. Dopamine inhibited binding with a potency similar to that previously found with standard membrane binding procedures. Autoradiography indicated that binding sites [3H](-)piquindone are localized to olfactory tubercle, accumbens nucleus, caudate putamen, cell bridges between caudate putamen and olfactory tubercle, and substantia nigra. Binding in these areas is stereoselective since we found no specific binding with [3H](+)piquindone, the biologically inactive enantiomer. Within caudate putamen, there was a lateral to medial gradient in the optical density of [3H](-)piquindone autoradiograms which might, in part, be attributable to white matter density rather than to D2 receptors.