Upregulation of the dorsal raphe nucleus-prefrontal cortex serotonin system by chronic treatment with escitalopram in hyposerotonergic Wistar-Kyoto rats

Makiko Yamada, Yukie Kawahara*, Fumi Kaneko, Yuki Kishikawa, Naoki Sotogaku, Wilfred J. Poppinga, Joost H. A. Folgering, Eliyahu Dremencov, Hiroshi Kawahara, Akinori Nishi

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Wistar-Kyoto (WKY) rats are sensitive to chronic stressors and exhibit depression-like behavior. Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons projecting to the prefrontal cortex (PFC) comprise the important neurocircuitry underlying the pathophysiology of depression. To evaluate the DRN-PFC 5-HT system in WKY rats, we examined the effects of escitalopram (ESCIT) on the extracellular 5-HT level in comparison with Wistar rats using dual-probe microdialysis. The basal levels of 5-HT in the DRN, but not in the PFC, in WKY rats was reduced as low as 30% of Wistar rats. Responses of 5-HT in the DRN and PFC to ESCIT administered systemically and locally were attenuated in WRY rats. Feedback inhibition of DRN 5-HT release induced by ESCIT into the PFC was also attenuated in WKY rats. Chronic ESCIT induced upregulation of the DRN-PFC 5-HT system in WRY rats, with increases in basal 5-HT in the DRN, responsiveness to ESCIT in the DRN and PFC, and feedback inhibition, whereas downregulation of these effects was induced in Wistar rats. Thus, the WRY rat is an animal model of depression with low activity of the DRN-PFC 5HT system. The finding that chronic ESCIT upregulates the 5-HT system in hyposerotonergic WRY rats may contribute to improved understanding of mechanisms of action of antidepressants, especially in depression with 5-HT deficiency. (C) 2013 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)169-178
Number of pages10
JournalNeuropharmacology
Volume72
Early online date3-May-2013
DOIs
Publication statusPublished - Sep-2013

Keywords

  • Microdialysis
  • Depression
  • Animal model
  • SSRIs
  • GENETIC ANIMAL-MODELS
  • IN-VIVO MICRODIALYSIS
  • ANTIDEPRESSANT TREATMENT
  • CHILDHOOD DEPRESSION
  • 5-HT1A RECEPTORS
  • WKY RATS
  • BEHAVIOR
  • STRESS
  • NEURONS
  • STRAINS

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