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

Although the involvement of both endogenous opioid and serotonergic systems in modulation of pain and emotion was suggested, the neurochemical interac tion between these systems in the brain has not previously been studied dir ectly. Herein, the effects of the local application of serotonin (5-MT) and fluoxetine (a 5-HT reuptake inhibitor) on extracellular levels of beta-end orphin in the arcuate nucleus and nucleus accumbens were assessed in freely moving rats using in vivo microdialysis. The mean basal concentrations of beta-endorphin in dialysates obtained from the arcuate nucleus and nucleus accumbens were 259.9 and 143.3 pM, respectively. Specific lesion of the ser otonergic system by 5,7-dihydroxytryptamine (5,7-DHT) caused a significant decrease in these dialysate beta-endorphin levels. When 5-HT (0.25-5 mu M) was added to the perfusion solution, the levels of beta-endorphin in the di alysate from the arcuate nucleus increased (186-296% of baseline), in a con centration-dependent manner. In the nucleus accumbens, 0.5 and 2 mu M 5-HT in the perfusion fluid did not affect the levels of beta-endorphin in the d ialysate, whereas 5 and 10 mu M 5-HT caused an increase of similar to 190% of baseline. When fluoxetine (250 mu M) was present in the perfusing soluti on, the levels of beta-endorphin in the dialysates from the arcuate nucleus and nucleus accumbens increased two- to threefold. This effect was not obt ained in the 5,7-DHT-lesioned rats. Thus, 5-MT, either endogenously or exog enously delivered, appears to facilitate the release of beta-endorphin in t he arcuate nucleus and nucleus accumbens. This indication of an interaction between serotonergic and endorphinic systems may be relevant far assessing pain and mood disorder circuits and the mode of action of antidepressant d rugs.