Effects of chronic neuroleptic treatment on agonist affinity states of the dopamine-D2 receptor in the rat brain.

The effects of repeated oral administration to rats of three antipsychotic compounds (haloperidol 1 mumol/kg, raclopride 5 mumol/kg and remoxipride 10 mumol/kg) on agonist affinity states of the dopamine-D2 receptor were studied using 3H-spiperone binding to rat striatal homogenates in vitro. The competition between 3H-spiperone and dopamine was analyzed using the iterative nonlinear computer program LIGAND. The treatment of rats with haloperidol, raclopride and remoxipride caused an increased number of striatal dopamine-D2 receptors. In parallel to this increase in Bmax (approximately 50%) there was an increased fraction of the number of receptors being in the D2 (high) affinity state. The affinity of dopamine for the D2 (high) state was not affected while a significant decrease in affinity of dopamine for the D2 (low) state was found. The results are discussed in view of the mechanism of action of the three compounds and of neuroleptics in general.