The anxiogenic drug FG-7142 increases serotonin metabolism in the rat medial prefrontal cortex

Andrew K. Evans, Jolane K. Abrams, J. Adriaan Bouwknecht, David M. Knight, Anantha Shekhar, Christopher A. Lowry

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The neural mechanisms underlying anxiety states are believed to involve interactions among forebrain limbic circuits and brainstem serotonergic systems. Consistent with this hypothesis, FG-7142, a partial inverse agonist at the benzodiazepine allosteric site of the GABAA receptor, increases c-Fos expression within a subpopulation of brainstem serotonergic neurons. Paradoxically, FG-7142 has no effect on extracellular serotonin concentrations, as measured using in vivo microdialysis, in certain anxiety-related brain structures. This study tested the hypothesis that FG-7142 alters serotonin metabolism within one or more nodes of a defined anxiety-related forebrain circuit. Rats received one of four treatments (vehicle, 1.9, 3.8, or 7.5 mg/kg FG-7142, i.p.) and brains were collected 1 h following treatment. Thirteen forebrain regions were microdissected and analyzed for l-tryptophan, serotonin, and 5-hydroxyindoleacetic acid concentrations using high pressure liquid chromatography with electrochemical detection. FG-7142 (7.5 mg/kg) increased l-tryptophan, serotonin, and 5-hydroxyindoleacetic acid concentrations in the prelimbic cortex but not in several other regions studied including subdivisions of the amygdala and bed nucleus of the stria terminalis. These data demonstrate that FG-7142 alters brain tryptophan concentrations and serotonin metabolism in specific components of an anxiety-related forebrain circuit including the medial prefrontal cortex, an important structure involved in executive function and the regulation of emotional behavior.

Original languageEnglish
Pages (from-to)266-274
Number of pages9
JournalPharmacology Biochemistry and Behavior
Volume84
Issue number2
DOIs
StatePublished - Jun 2006

Fingerprint

Prefrontal Cortex
Metabolism
Rats
Serotonin
Prosencephalon
Anxiety
Tryptophan
Pharmaceutical Preparations
Brain
Hydroxyindoleacetic Acid
Brain Stem
Networks (circuits)
High pressure liquid chromatography
Allosteric Site
Serotonergic Neurons
Septal Nuclei
Executive Function
Microdialysis
GABA-A Receptors
Amygdala

Keywords

  • Anxiety
  • FG-7142
  • l-tryptophan
  • Medial prefrontal cortex
  • Serotonin

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

The anxiogenic drug FG-7142 increases serotonin metabolism in the rat medial prefrontal cortex. / Evans, Andrew K.; Abrams, Jolane K.; Bouwknecht, J. Adriaan; Knight, David M.; Shekhar, Anantha; Lowry, Christopher A.

In: Pharmacology Biochemistry and Behavior, Vol. 84, No. 2, 06.2006, p. 266-274.

Research output: Contribution to journalArticle

Evans, Andrew K. ; Abrams, Jolane K. ; Bouwknecht, J. Adriaan ; Knight, David M. ; Shekhar, Anantha ; Lowry, Christopher A. / The anxiogenic drug FG-7142 increases serotonin metabolism in the rat medial prefrontal cortex. In: Pharmacology Biochemistry and Behavior. 2006 ; Vol. 84, No. 2. pp. 266-274.
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