Impaired release of β-endorphin in response to serotonin in a rat model of depression

A. Zangen, R. Nakash, I. Roth-Deri, D. H. Overstreet, G. Yadid

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Involvement of both the serotonergic and the endogenous opioid systems in the onset of depressive behavior has been suggested. Previously we showed that serotonin (5-hydroxytryptamine) facilitates β-endorphin release in the nucleus accumbens (NAcc). Herein, the microdialysis method was used to assess in vivo the effects of serotonin on β-endorphin release in a rat model of depressive behavior (the Flinders sensitive line, FSL), before and after antidepressant treatment. The basal extracellular level of β-endorphin in the NAcc of FSL rats did not differ significantly from that in control rats. However, serotonin-induced β-endorphin release was impaired in FSL rats. Chronic treatment (18 days) with desipramine or paroxetine did not significantly affect the extracellular levels of β-endorphin in the NAcc of either the FSL or control rats. However, the chronic antidepressant treatment did normalize the serotonin-induced release of β-endorphin in FSL rats, as well as their behavioral manifestation of depressive behavior. Our results show that depressive behavior may relate to an impaired effect of serotonin on β-endorphin release in the NAcc in a rat model of depression, and suggest a possible new mode of action of antidepressant drugs.

Original languageEnglish
Pages (from-to)389-393
Number of pages5
Issue number3
StatePublished - 20 Mar 2002

Bibliographical note

Funding Information:
This study was in part funded by the National Institute of Psychobiology in Israel and the Israel Academy of Science and Humanities.


  • Depression
  • Microdialysis
  • Nucleus accumbens
  • Serotonin
  • β-endorphin


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