Decreased [(3)H]spiperone binding in the anterior cingulate cortex of schizophrenia patients: an autoradiographic study.
Abnormalities in the anterior cingulate cortex have been reported in patients with schizophrenia, and have been implicated in the pathophysiology of this disorder. In the present study, we have examined antipsychotic-sensitive binding sites in the left anterior cingulate cortex of schizophrenia patients and controls. Using quantitative autoradiography and [(3)H]spiperone as a ligand, both saturation and competition experiments were performed in post-mortem brain tissue obtained from six schizophrenia and six control cases. Saturation experiments revealed that the maximum number of [(3)H]spiperone binding sites was significantly reduced by 31% in the schizophrenia group as compared to the control group (65.3+/-5.6 fmol/mg tissue versus 94.2+/-7.3 fmol/mg tissue). Increased dissociation constant was also observed in the schizophrenia group (2.2+/-0.4 nM versus 1.3+/-0.2 nM), but was not statistically significant (P=0.07). Competition experiments were performed in order to examine the pharmacological profile of [(3)H]spiperone binding, and revealed that: (i) displacement of [(3)H]spiperone binding by clozapine and mianserin was significantly reduced in the schizophrenia group as compared to the control group (-26% and -16% respectively); (ii) the order of displacement potency of the drugs tested was: haloperidol>mianserin>butaclamol approximately risperidone>clozapine>2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene. Our results suggest a reduction of antipsychotic-sensitive binding sites in the anterior cingulate cortex of patients with schizophrenia. Such abnormality could lead to an imbalance in neurotransmitter regulation in the anterior cingulate cortex which may contribute to the emergence of some symptoms of schizophrenia.
Zavitsanou
K
K
Neuroscience Institute of Schizophrenia and Allied Disorders and Metabolic Research Centre, Department of Biomedical Sciences, University of Wollongong, Wollongong, NSW 2522, Australia. katerina_zavitsanou@uow.edu.au
Huang
X F
XF
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D002069:Butaclamol; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006220:Haloperidol; D006801:Humans; D008803:Mianserin; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011869:Radioligand Assay; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D018967:Risperidone; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013134:Spiperone; D014316:Tritium
D014150:Antipsychotic Agents; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D014316:Tritium; D008803:Mianserin; D013134:Spiperone; D002069:Butaclamol; D006220:Haloperidol; D018967:Risperidone