Serotonin-1A receptor function in the dorsal raphe nucleus following chronic administration of the selective serotonin reuptake inhibitor sertraline

Dania V. Rossi, Teresa F. Burke, Melissa McCasland, Julie G. Hensler

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Serotonin-1A (5-HT1A) receptors in the dorsal raphe nucleus (DRN) function as somatodendritic autoreceptors, and therefore play a critical role in controlling serotonergic cell firing and serotonergic neurotransmission. We hypothesized that a decrease in the capacity of 5-HT1A receptors to activate G proteins was a general mechanism by which 5-HT1A receptors in the DRN are desensitized following chronic administration of selective serotonin reuptake inhibitors (SSRIs). Using in vivo microdialysis, we found that the ability of the 5-HT1A receptor agonist 8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT) (0.025 mg/kg, s.c.) to decrease extracellular 5-HT levels in striatum was attenuated following chronic treatment of rats with the SSRIs sertraline or fluoxetine. This apparent desensitization of somatodendritic 5-HT1A autoreceptor function was not accompanied by a decrease in 5-HT1A receptor sites in the coupled, high-affinity agonist state as measured by the binding of [3H]8-OH-DPAT. In marked contrast to what was observed following chronic administration of fluoxetine, 5-HT1A receptor-stimulated [ 35S]GTPγS binding in the DRN was not altered following chronic sertraline treatment. Thus, desensitization of 5-HT1A somatodendritic autoreceptor function following chronic sertraline administration appears not to be due to a decrease in the capacity 5-HT1A receptors to activate G proteins in the DRN. Our findings suggest that the SSRIs may not be a homogeneous class of antidepressant drug with regard to the mechanism by which the function of somatodendritic 5-HT1A autoreceptors is regulated.

Original languageEnglish (US)
Pages (from-to)1091-1099
Number of pages9
JournalJournal of neurochemistry
Volume105
Issue number4
DOIs
StatePublished - May 2008

Keywords

  • In vivo microdialysis
  • Quantitative autoradiography
  • Serotonin transporter binding
  • [S]GTPγS binding

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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