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Alterations of muscarinic and GABA receptor binding in the posterior cingulate cortex in schizophrenia.

Abstract
The posterior cingulate cortex (PCC), a key component of the limbic system, has been implicated in the pathology of schizophrenia because of its sensitivity to NMDA receptor antagonists. Recent studies have shown that the PCC is dysfunctional in schizophrenia, and it is now suspected to be critically involved in the pathogenesis of schizophrenia. Studies also suggest that there are abnormalities in muscarinic and GABAergic neurotransmission in schizophrenia. Therefore, in the present study we used quantitative autoradiography to investigate the binding of [(3)H]pirenzepine, [(3)H]AF-DX 384 and [(3)H]muscimol, which respectively label M1/4 and M2/4 muscarinic and GABA(A) receptors, in the PCC of schizophrenia and control subjects matched for age and post-mortem interval. The present study found that [(3)H]pirenzepine binding was significantly decreased in the superficial (-24%, p=0.002) and deep (-35%, p<0.001) layers of the PCC in the schizophrenia group as compared with the control group. In contrast, a dramatic increase in [(3)H]muscimol binding was observed in the superficial (+112%, p=0.001) and deep layers (+100%, p=0.017) of the PCC in the schizophrenia group. No difference was observed for [(3)H]AF-DX 384 binding between the schizophrenia and control groups. The authors found a significant inverse correlation between [(3)H]pirenzepine binding in the deep cortical layers and [(3)H]muscimol binding in the superficial layers (rho=-0.732, p=0.003). In addition, negative correlations were also found between age and [(3)H]pirenzepine binding in both superficial and deep cortical layers (rho=-0.669 p=0.049 and rho=-0.778, p=0.014), and between age of schizophrenia onset and [(3)H]AF-DX 384 binding (rho=-0.798, p=0.018). These results for the first time demonstrated the status of M1/M4, M2/M4 and GABA(A) receptors in the PCC in schizophrenia. Whilst the exact mechanism causing these alterations is not yet known, a possible increased acetylcholine and down regulated GABA stimulation in the PCC of schizophrenia is suggested.
AuthorsKelly A Newell, Katerina Zavitsanou, Stephen Kum Jew, Xu-Feng Huang
JournalProgress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 31 Issue 1 Pg. 225-33 (Jan 30 2007) ISSN: 0278-5846 [Print] England
PMID16901598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • GABA Agonists
  • Muscarinic Antagonists
  • Receptors, GABA
  • Receptors, Muscarinic
  • AFDX 384
  • Muscimol
  • Pirenzepine
Topics
  • Adult
  • Aged
  • Autoradiography
  • Female
  • GABA Agonists (metabolism)
  • Gyrus Cinguli (metabolism)
  • Humans
  • Male
  • Middle Aged
  • Muscarinic Antagonists (metabolism)
  • Muscimol (metabolism)
  • Pirenzepine (analogs & derivatives, metabolism)
  • Receptors, GABA (metabolism)
  • Receptors, Muscarinic (metabolism)
  • Schizophrenia (metabolism)

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