Binding of ³H-neuroleptics and ³H-apomorphine in schizophrenic brains

Abstract

THE neuroleptic or antipsychotic drugs, introduced in 1952¹, effectively prevent relapse and rehospitalisation of schizophrenic patients. These drugs provide a strategy² for localising possible abnormalities in the brain in schizophrenia. The hypothesis that schizophrenia might be associated with abnormally sensitive dopamine synapses^3–6 evolved from the suggestion that neuroleptics block dopamine receptors and thus accelerate the turnover of dopamine^7,8. The hypothesis received additional support from the observations that dopamine-mimetic drugs (for example d-amphetamine, L-dopa) elicit or exacerbate psychotic symptoms^9–12, that neuroleptics produce supersensitivity to dopamine^13–15, that the neuroleptic and antipsychotic actions are enhanced by drugs which block the synthesis of catecholamines¹⁶, that neuroleptics all have conformations that match that of dopamine¹⁷, and that dopamine is the most potent neurotransmitter to inhibit the specific binding of ³H-haloperidol to dopamine-rich regions of the brain^18–20. Although all this evidence for the dopamine hypothesis of schizophrenia is circumstantial, we have now obtained direct evidence for some abnormalities in brain dopamine receptors in schizophrenia by measuring the specific binding of ³H-apomorphine and ³H-haloperidol or ³H-spiperone to four regions of postmortem brains from schizophrenic patients.