Endorphins, Dopamine, and Schizophrenia*

The theory that alterations of dopaminergic synaptic transmission may play a role in the pathogenesis of schizophrenia is widely accepted. A more recent theory links the endorphin system to the etiology of schizophrenia. We propose that these two theories may be combined into a single model. Recent neurochemical and pharmacological findings have indicated close functional relationships between the endorphin and dopamine systems. Endorphins modulate dopaminergic synaptic transmission by exerting both presynaptic and postsynaptic effects. On the molecular level, this modulation may involve the activity of nucleotide cyclases and protein phosphorylation systems. Thus, the dopaminergic neuronal hyperactivity, currently believed to be related to schizophrenia, may be caused by a primary alteration in the endorphin system. Several hypotheses about the nature of that alteration have been advanced and tested in therapeutic experiments with schizophrenic patients. These experiments have not yet yielded definitive results.