title: Metabotropic glutamate receptor 5 binding and protein expression in schizophrenia and following antipsychotic drug treatment.
abstract: Metabotropic glutamate receptor 5 (mGluR5) has been identified as a potential therapeutic target for schizophrenia, primarily due to its ability to indirectly modulate glutamatergic signalling through the NMDA receptor (NMDAR). Despite its potential, molecular studies characterising mGluR5 in schizophrenia are limited. We therefore aimed to determine if the mGluR5 binding site or protein levels were altered in schizophrenia or by current antipsychotics. Using in-situ radioligand binding and immunoblot, we measured [(3)H]MPEP binding to mGluR5 and mGluR5 protein density in the post-mortem dorsolateral prefrontal cortex (DLPFC; BA46) of 37 schizophrenia and 37 matched control subjects. Subsequently, we measured [(3)H]MPEP binding in rat brains following typical (haloperidol) or atypical (olanzapine) antipsychotic treatment (n = 6/group). Subjects with schizophrenia showed no significant alteration in mGluR5 binding density or mGluR5 protein levels. Furthermore, mGluR5 binding in the rat cortex, thalamus, hippocampus and striatum was unaltered by short-, medium- and long-term antipsychotic treatment. Our data suggests that there are no alterations in mGluR5 in schizophrenia subjects. The lack of alteration in mGluR5 binding and protein in schizophrenia is advantageous because its ability to modulate the NMDAR is potentially unhindered, thereby supporting the development of novel antipsychotic agents that work through the mGluR5/NMDAR complex.
authors: Centre for Translational Neuroscience, Illawarra Health and Medical Research Institute, School of Health Sciences, University of Wollongong, NSW 2522, Australia. natalie_matosin@uow.edu.au
authors: Natalie
authors: N
authors: Matosin
authors: Elisabeth
authors: E
authors: Frank
authors: Chao
authors: C
authors: Deng
authors: Xu-Feng
authors: XF
authors: Huang
authors: Kelly A
authors: KA
authors: Newell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology*; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; C578935:GRM5 protein, human; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D014316:Tritium; C121465:6-methyl-2-(phenylethynyl)pyridine