THE DENSITY OF MUSCARINIC M(1) RECEPTORS IS DECREASED IN THE CAUDATE-PUTAMEN OF SUBJECTS WITH SCHIZOPHRENIA

Changes in cholinergic neurons have been implicated in the pathology o f schizophrenia, Clozapine, an atypical anti-psychotic drug, has been shown to bind with high affinity to the muscarinic(1) (M(1)) receptor suggesting this receptor could be involved in the therapeutic efficacy of the drug, Because of this we measured the density of M(1) receptor s in the caudate-putamen, obtained at autopsy, from 19 schizophrenic s ubjects and 19 non-schizophrenic subjects, The density of M(1) recepto rs was decreased in the caudate-putamen from the schizophrenic subject s (181 +/- 20 vs 287 +/- 10 fmol mg(-1) TE; mean +/- s.e.m.; P < 0.001 ), Furthermore, preliminary studies would not suggest that the change in the density of M(1) receptors in the tissue from the schizophrenic subjects had resulted from drug treatment prior to death, These data r aise the possibility that changes in muscarinic receptors may be invol ved in the pathology of schizophrenia.