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

Neuroscience. 2002;110(3):389-93. doi: 10.1016/s0306-4522(01)00612-1.


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 beta-endorphin release in the nucleus accumbens (NAcc). Herein, the microdialysis method was used to assess in vivo the effects of serotonin on beta-endorphin release in a rat model of depressive behavior (the Flinders sensitive line, FSL), before and after antidepressant treatment. The basal extracellular level of beta-endorphin in the NAcc of FSL rats did not differ significantly from that in control rats. However, serotonin-induced beta-endorphin release was impaired in FSL rats. Chronic treatment (18 days) with desipramine or paroxetine did not significantly affect the extracellular levels of beta-endorphin in the NAcc of either the FSL or control rats. However, the chronic antidepressant treatment did normalize the serotonin-induced release of beta-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 beta-endorphin release in the NAcc in a rat model of depression, and suggest a possible new mode of action of antidepressant drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / pharmacology
  • Depression / drug therapy
  • Depression / metabolism*
  • Depression / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism*
  • Male
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Serotonin / pharmacology
  • Serotonin Uptake Inhibitors / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • beta-Endorphin / metabolism*


  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors
  • Serotonin
  • beta-Endorphin