Research article summary (published 6 Aug 2007):

In vivo/ex vivo and behavioural study on central effects of 5-HT1B/1D and 5-HT1A antagonists in guinea pigs.

Full Abstract

Serotonin 5-HT1A and 5-HT1B/1D receptors control serotonin (5-HT) release and are targets for the pharmacological treatment of psychiatric disorders. We investigated effects of the 5-HT1B/1D antagonist GR127935, the 5-HT1A antagonist WAY 100635 and a combination of both in guinea pigs on the behaviour in the forced swimming test and on extracellular 5-HT in the hippocampus and the prefrontal cortex using in vivo microdialysis. Tissue content of 5-HT, 5-HIAA and 5-HT turnover (ratio 5-HIAA/5-HT) were determined in a sample containing i) the median and dorsal raphe nuclei, ii) the frontal cortex, or iii) the ventral hippocampus ex vivo. BEHAVIOUR: Administration of WAY 100635 (0.3-3.0 mg/kg, i.p.) or GR127935 (1.0-10.0 mg/kg, i.p.) or the combination of both delayed immobility in the forced swim test. MICRODIALYSIS: Systemic administration of WAY 100635 (1 mg/kg i.p.), perfusion with GR127935 (10 microM perfused into the frontal cortex) in the medial prefrontal cortex or the combination of both treatments had no significant effect on extracellular 5-HT. 5-HT TISSUE CONTENT AND 5-HT TURNOVER IN THE TISSUE: Compared to controls, WAY 100635, GR127935 and the combination thereof, decreased cortical 5-HT (-30%), increased 5-HIAA and consequently 5-HT turnover in the cortex threefold and the raphe nuclei twofold. WAY 100635 decreased 5-HT in the hippocampus (-40%), too. WAY 100635 and GR127935 and their combination increased hippocampal 5-HIAA and 5-HT turnover twofold, compared to controls. The results suggest that both 5-HT1 antagonists have subtle effects on 5-HT function under resting conditions; combined treatment has no superior effects compared to solitary treatment.

Author information

Author/s: Rex, A (A); Voigt, J P (JP); Wicke, K M (KM); Fink, H (H);

Affiliation: Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Koserstr. 20, 14195 Berlin, Germany. rex.andre(-atsign-)vetmed.fu-berlin.de <rex.andre(-atsign-)vetmed.fu-berlin.de>

Journal and publication information

Publication Type: Journal Article

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

Reference: 2008-Jan; vol 88 (issue 3) : pp 196-204

Dates: Created 2007/11/23; Completed 2008/04/09;

PMID: 17888505, 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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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Behavior, Animal - drug effects Brain Chemistry - drug effects Depression - psychology Female Guinea Pigs Hydroxyindoleacetic Acid - metabolism Microdialysis Oxadiazoles - pharmacology

Oxadiazoles - pharmacology Piperazines - pharmacology Pyridines - pharmacology Receptor, Serotonin, 5-HT1A - drug effects Receptor, Serotonin, 5-HT1B - drug effects Receptor, Serotonin, 5-HT1D - drug effects Serotonin - metabolism Serotonin Antagonists - pharmacology Swimming - psychology

Associated Chemicals: Oxadiazoles (0) ; Piperazines (0) ; Pyridines (0) ; Receptor, Serotonin, 5-HT1B (0) ; Receptor, Serotonin, 5-HT1D (0) ; Serotonin Antagonists (0) ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; WAY 100635 (146714-97-8) ; GR 127935 (148672-13-3) ; Serotonin (50-67-9) ; Hydroxyindoleacetic Acid (54-16-0)

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