Serotonin-mediated increases in the extracellular levels of β-endorphin in the arcuate nucleus and nucleus accumbens: A microdialysis study

Abraham Zangen, Rachel Nakash, Gal Yadid

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Although the involvement of both endogenous opioid and serotonergic systems in modulation of pain and emotion was suggested, the neurochemical interaction between these systems in the brain has not previously been studied directly. Herein, the effects of the local application of serotonin (5-HT) and fluoxetine (a 5-HT reuptake inhibitor) on extracellular levels of β-endorphin in the arcuate nucleus and nucleus accumbens were assessed in freely moving rats using in vivo microdialysis. The mean basal concentrations of β-endorphin in dialysates obtained from the arcuate nucleus and nucleus accumbens were 259.9 and 143.3 pM, respectively. Specific lesion of the serotonergic system by 5,7-dihydroxytryptamine (5,7-DHT) caused a significant decrease in these dialysate β-endorphin levels. When 5-HT (0.25-5 μM) was added to the perfusion solution, the levels of β-endorphin in the dialysate from the arcuate nucleus increased (186-296% of baseline), in a concentration-dependent manner. In the nucleus accumbens, 0.5 and 2 μM 5-HT in the perfusion fluid did not affect the levels of β-endorphin in the dialysate, whereas 5 and 10 μM 5-HT caused an increase of ~190% of baseline. When fluoxetine (250 μM) was present in the perfusing solution, the levels of β-endorphin in the dialysates from the arcuate nucleus and nucleus accumbens increased two- to three-fold. This effect was not obtained in the 5,7-DHT-lesioned rats. Thus, 5-HT, either endogenously or exogenously delivered, appears to facilitate the release of β-endorphin in the arcuate nucleus and nucleus accumbens. This indication of an interaction between serotonergic and endorphinic systems may be relevant for assessing pain and mood disorder circuits and the mode of action of antidepressant drugs.

Original languageEnglish
Pages (from-to)2569-2574
Number of pages6
JournalJournal of Neurochemistry
Volume73
Issue number6
DOIs
StatePublished - 29 Nov 1999
Externally publishedYes

Keywords

  • Arcuate nucleus
  • Fluoxetine
  • Microdialysis
  • Nucleus accumbens
  • Serotonin
  • β-Endorphin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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