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

Full 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.

Author information

Author/s: Evans, Andrew K (AK); Abrams, Jolane K (JK); Bouwknecht, J Adriaan (JA); Knight, David M (DM); Shekhar, Anantha (A); Lowry, Christopher A (CA);

Affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Bristol BS1 3NY, UK. a.evans(-atsign-)bristol.ac.uk

Grants: R01 MH065702 (Agency:NIMH NIH HHS) ; R01 MH52619 (Agency:NIMH NIH HHS) ; RCDF 068558/Z/02/Z (Agency:Wellcome Trust)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav), published in United States. (Language: eng)

Reference: 2006-Jun; vol 84 (issue 2) : pp 266-74

Dates: Created 2006/07/31; Completed 2006/10/05; Revised 2007/11/14;

PMID: 16784772, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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