ENDOGENOUSLY RELEASED DOPAMINE INHIBITS THE BINDING OF DOPAMINERGIC PET AND SPECT LIGANDS IN SUPERFUSED RAT STRIATAL SLICES

Pharmacologically induced changes in synaptic levels of dopamine (DA) have been found, in some studies, to affect the in vivo binding of dop aminergic radioligands. In the present study we used a superfused brai n slice preparation to examine the effect of synaptically released dop amine on the binding of some commonly used PET and SPECT radioligands under more controlled conditions than those present in vivo. The relea se of DA was evoked by electrical stimulation of striatal slices and t he sensitivity of binding of the D-1 receptor ligand, [H-3]SCH 23390, the D-2 receptor ligands [H-3]raclopride and [I-123]epidepride, and th e DA uptake transporter ligands, [H-3]WIN 35,428 and [I-123]RTI-55, to the frequency of stimulation examined. Most affected by stimulation w as the specific binding of [H-3]SCH 23390, which was fully inhibited a t 2.5 Hz. This was followed by [H-3]raclopride and [I-123]epidepride, respectively, the binding of the latter showing only a 50% reduction a t the highest frequency of 10 Hz. [H-3]WIN 35,428 and [I-123]RTI-55 bi nding was unaffected by stimulation. The effects of stimulation on [H- 3]raclopride binding were prevented by reserpine pretreatment of the r at, when combined with inclusion of the dopamine synthesis inhibitor, alpha-methyl-p-tyrosine, in the superfusate medium. We conclude that, in-brain slices, the binding of D-1 and D-2 receptor ligands but not t hat of DA uptake transporter ligands is readily inhibited by DA releas ed into the synaptic cleft. Brain slices may prove to be a useful mode l system for the investigation of factors affecting competition betwee n radioligand binding and endogenous neurotransmitters. (C) 1996 Wiley -Liss, Inc.