Dopamine Receptor Changes in Schizophrenia in Relation to the Disease Process and Movement Disorder

Abstract

Although dopamine receptor antagonism probably accounts for the therapeutic efficacy of neuroleptic drugs in schizophrenia, there is little evidence to suggest that dopamine neurones are overactive (Bowers, 1974; Owen et al. 1978; Bird et al., 1979). An alternative concept is that abnormalities exist in post-synaptic dopamine receptors (Bowers, 1974; Crow et al., 1976). The binding of butyrophenone neuroleptics to dopamine receptors has been reported to be increased in post-mortem brains of schizophrenics in several independant studies (Owen et al., 1978; Lee et al., 1978; Mackay et al., 1982). These findings raise a number of crucial issues: 1. How specific is the increase in dopamine receptors in relation to other neurotransmitter receptors, and also in the context of dopamine receptor heterogeneity, 2. Is the increase in dopamine receptors observed in schizophrenics entirely due to the effects of chronic neuroleptic treatment, and 3. Do the increases observed in dopamine receptors in schizophrenics relate to specific features of the disease. Since our initial report of increased ³H-spiperone binding to brains of schizophrenics (Owen et al., 1978), we have attempted to investigate each of these aspects, using a larger series of post-mortem brains from control subjects and schizophrenics, some of whom had been assessed clinically prior to death.