Reduced 5-HT1A- and GABAB receptor function in dorsal raphé neurons upon chronic fluoxetine treatment of socially stressed rats

L. N. Cornelisse, J. E. Van Der Harst, J. C. Lodder, P. J.J. Baarendse, A. J. Timmerman, H. D. Mansvelder, B. M. Spruijt, A. B. Brussaard*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Autoinhibitory serotonin 1A receptors (5-HT1A) in dorsal raphé nucleus (DRN) have been implicated in chronic depression and in actions of selective serotonin reuptake inhibitors (SSRI). Due to experimental limitations, it was never studied at single-cell level whether changes in 5-HT1A receptor functionality occur in depression and during SSRI treatment. Here we address this question in a social stress paradigm in rats that mimics anhedonia, a core symptom of depression. We used whole cell patch-clamp recordings of 5-HT- and baclophen-induced G-protein-coupled inwardly rectifying potassium (GIRK) currents as a measure of 5-HT1A- and GABAB receptor functionality. 5-HT1A- and GABAB receptor-mediated GIRK-currents were not affected in socially stressed rats, suggesting that there was no abnormal (auto)inhibition in the DRN on social stress. However, chronic fluoxetine treatment of socially stressed rats restored anticipatory behavior and reduced the responsiveness of 5-HT1A receptor-mediated GIRK currents. Because GABAB receptor-induced GIRK responses were also suppressed, fluoxetine does not appear to desensitize 5-HT1A receptors but rather one of the downstream components shared with GABAB receptors. This fluoxetine effect on GIRK currents was also present in healthy animals and was independent of the animal's "depressed" state. Thus our data show that symptoms of depression after social stress are not paralleled by changes in 5-HT1A receptor signaling in DRN neurons, but SSRI treatment can alleviate these behavioral symptoms while acting strongly on the 5-HT1A receptor signaling pathway.

Original languageEnglish
Pages (from-to)196-204
Number of pages9
JournalJournal of Neurophysiology
Volume98
Issue number1
DOIs
Publication statusPublished - 1 Jul 2007
Externally publishedYes

Cite this