Impaired release of beta-endorphin in response to serotonin in a rat model of depression.
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.
Zangen
A
A
Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Nakash
R
R
Roth-Deri
I
I
Overstreet
D H
DH
Yadid
G
G
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D001615:beta-Endorphin / Q000378:metabolism*
D000929:Antidepressive Agents, Tricyclic; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D001615:beta-Endorphin