Do antipsychotic drugs and serotonin down regulate [ 3H]-spiroperidol binding sites in human cortex?

[ 3H]-Spiroperidol binds at several specific sites in postmortem human prefrontal cortex at 21°C (1). The overall selectivity of these sites is serotonergic (1). At 37°C, there is a marked loss of specific [ 3H]-spiroperidol binding that occurs between 10 and 60 min (1). This loss of binding is not apparently due to 3H-ligand degeneration or metabolism, or to non-specific binding site degradation. The loss of binding can also be produced by serotonin (5-HT), haloperidol and chlorpromazine but not by prazosin. The rate of the loss of binding is dependent on 3H-ligand concentration and protein concentration. The loss of binding is correlated with a loss of serotonin selective [ 3H]-spiroperidol binding sites having a K D of approximately 0.04 nM. Therefore antipsychotic compounds and 5-HT appear to down-regulate a subset of antipsychotic binding sites in human prefrontal cortex.