title: Behavioral sensitization to methamphetamine induces specific interneuronal mRNA pathology across the prelimbic and orbitofrontal cortices.
abstract: Schizophrenia is associated with significant pathophysiological changes to interneurons within the prefrontal cortex (PFC), with mRNA and protein changes associated with the GABA network localized to specific interneuron subtypes. Methamphetamine is a commonly abused psychostimulant that can induce chronic psychosis and symptoms that are similar to schizophrenia, suggesting that chronic METH induced psychosis may be associated with similar brain pathology to schizophrenia in the PFC. The aim of this study, therefore, was to examine mRNA expression of interneuron markers across two regions of the PFC (prelimbic (PRL) and orbitofrontal cortices (OFC)) following METH sensitization, an animal model of METH psychosis. We also studied the association between GABA mRNA expression and interneuronal mRNA expression to identify whether particular changes to the GABA network could be localized to a specific inhibitory cellular phenotype. METH sensitization increased the transcriptional expression of calbindin, calretinin, somatostatin, cholecyctokinin and vasoactive intestinal peptide in the PRL while parvalbumin, calbindin, cholectokinin and vasoactive intestinal peptide were upregulated in the OFC. Based on our previous findings, we also found significant correlations between GAD67, GAT1and parvalbumin while GAD67, GAD65and GAT1were positively correlated with cholecystokinin in the PRL of METH sensitized rats. Within the OFC, the expression of GABAAα1 was positively correlated with somatostatin while GABAAα5 was negatively associated with somatostatin and calbindin. These findings suggest that METH sensitization differentially changes the expression of mRNAs encoding for multiple peptides and calcium binding proteins across the PRL and the OFC. Furthermore, these findings support that changes to the GABA network may also occur within specific cell types. These results, therefore, provide the first evidence that METH sensitization mediates differential interneuronal pathology across the PRL and OFC and such changes could have profound consequences on behavior and cognitive output.
authors.affiliation: Department of Psychology, Faculty of Human Sciences, Centre for Emotional Health, Macquarie University, Sydney, NSW, Australia.
authors.forename: Travis A
authors.initials: TA
authors.lastname: Wearne
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Science, Macquarie University, Sydney, NSW, Australia; ARC Center of Excellence for Nanoscale BioPhotonics, Macquarie University, Sydney, NSW, Australia.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Parker
authors.affiliation: Department of Psychology, Faculty of Human Sciences, Centre for Emotional Health, Macquarie University, Sydney, NSW, Australia.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Franklin
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Science, Macquarie University, Sydney, NSW, Australia.
authors.forename: Ann K
authors.initials: AK
authors.lastname: Goodchild
authors.affiliation: Department of Psychology, Faculty of Human Sciences, Centre for Emotional Health, Macquarie University, Sydney, NSW, Australia; ARC Center of Excellence for Nanoscale BioPhotonics, Macquarie University, Sydney, NSW, Australia. Electronic address: jennifer.cornish@mq.edu.au.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cornish
mesh_terms: D000818:Animals; D059333:Central Nervous System Sensitization; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology*; D065726:Limbic Lobe / Q000378:metabolism* / Q000473:pathology; D008694:Methamphetamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011963:Receptors, GABA-A / Q000096:biosynthesis; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; C546241:Gabra1 protein, mouse; C496250:Gabra5 protein, mouse; D009419:Nerve Tissue Proteins; D010455:Peptides; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D008694:Methamphetamine; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2