3H-flupenthixol binding in post-mortem brains of schizophrenics: Evidence for a selective increase in dopamine D2 receptors

The binding of ³H-cis flupenthixol (³H-FPT) to dopamine receptors in membrane preparations from control subjects and schizophrenics was studied. Using a fixed concentration of ³H-FPT, no differences were observed between controls and all schizophrenics, although ³H-FPT binding was increased in schizophrenics who apparently were drug-free at the time of death. Scatchard analysis of ³H-FPT binding revealed that in drug-treated schizophrenics both the number of binding sites (B_M) and the dissociation constant (K_D) were increased, whilst in drug-free schizophrenics only the B_M was increased. Using domperidone to differentiate ³H-FPT binding to D1 and D2 dopamine sites, it was found that only D2 sites were increased in drug-free schizophrenics. The results are discussed with reference to previous studies on dopamine receptors in schizophrenia, and the effects of neuroleptic treatment. It is suggested that a selective increase in D2 receptors may be associated with the disease process in schizophrenia.