GABAergic mRNA expression is differentially expressed across the prelimbic and orbitofrontal cortices of rats sensitized to methamphetamine

Relevance to psychosis

Travis A. Wearne, Lindsay M. Parker, Jane L. Franklin, Ann K. Goodchild, Jennifer L. Cornish*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Psychotic disorders, such as schizophrenia, are characterized by prevalent and persistent executive deficits that are believed to be the result of dysfunctional inhibitory gamma-aminobutyric acid (GABA) processing of the prefrontal cortex (PFC). Methamphetamine (METH) is a commonly used psychostimulant that can induce psychotic and cognitive symptoms that are indistinguishable to schizophrenia, suggesting that METH-induced psychosis may have a similar GABAergic profile of the PFC. As the PFC consists of multiple subregions, the aim of the current study was to investigate changes to GABAergic mRNA expression in the prelimbic (PRL) and orbitofrontal (OFC) cortices of the PFC in rats sensitized to repeated METH administration. Male Sprague Dawley rats underwent daily METH or saline injections for 7 days. Following 14 days of withdrawal, rats were challenged with acute METH administration, RNA was isolated from the PRL and OFC and quantitative PCR was used to compare the relative expression of GABA enzymes, transporters, metabolites and receptor subunits. GAD67, GAD65, GAT1, GAT3, VGAT and GABAT mRNA expression were upregulated in the PRL. Ionotropic GABAA receptor subunits α1, α3, α5 and β2 were specifically upregulated in the OFC. These findings suggest that alterations to GABAergic mRNA expression following sensitization to METH are biologically dissociated between the OFC and PRL, suggesting that GABAergic gene expression is significantly altered following chronic METH exposure in a brain-region and GABA-specific manner. These changes may lead to profound consequences on central inhibitory mechanisms of localized regions of the PFC and may underpin common behavioral phenotypes seen across psychotic disorders.

Original languageEnglish
Pages (from-to)107-118
Number of pages12
JournalNeuropharmacology
Volume111
DOIs
Publication statusPublished - 1 Dec 2016

Keywords

  • Methamphetamine
  • Sensitization
  • GABA
  • Prefrontal cortex
  • Psychosis
  • Schizophrenia
  • GAMMA-AMINOBUTYRIC-ACID
  • DORSOLATERAL PREFRONTAL CORTEX
  • ANTERIOR CINGULATE CORTEX
  • INDUCED BEHAVIORAL SENSITIZATION
  • LONG-TERM ABSTINENCE
  • GABA(A) RECEPTORS
  • REPEATED AMPHETAMINE
  • GENE-EXPRESSION
  • PARANOID SCHIZOPHRENIA
  • COGNITIVE DYSFUNCTION

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