Therapeutic treatment with fluoxetine using the chronic unpredictable stress model induces changes in neurotransmitters and circulating miRNAs in extracellular vesicles.

The most widely prescribed antidepressant, fluoxetine (FLX), is known for its antioxidant and anti-inflammatory effects when administered post-stress. Few studies have evaluated the effects of FLX treatment when chronic stress has induced deleterious effects in patients. Our objective was to evaluate FLX treatment (20 mg/kg/day, i.v.) once these effects are manifested, and the drug's relation to extracellular circulating microRNAs associated with inflammation, a hedonic response (sucrose intake), the forced swim test (FST), and corticosterone levels (CORT) and monoamine concentrations in limbic areas. A group of Wistar rats was divided into groups: Control; FLX; CUMS (for six weeks of exposure to chronic, unpredictable mild stress); and CUMS + FLX, a mixed group. After CUMS, the rats performed the FST, and serum levels of CORT and six microRNAs (miR-16, -21, -144, -155, -146a, -223) were analyzed, as were levels of dopamine, noradrenaline, and serotonin in the prefrontal cortex, hippocampus, and hypothalamus. CUMS reduced body weight, sucrose intake, and hippocampal noradrenaline levels, but increased CORT, immobility behavior on the FST, dopamine concentrations in the prefrontal cortex, and all miRNAs except miR-146a expression. Administering FLX during CUMS reduced CORT levels and immobility behavior on the FST and increased the expression of miR-16, -21, -146a, -223, and dopamine. FLX protects against the deleterious effects of stress by reducing CORT and has an antidepressant effect on the FST, with minimally-modified neurotransmitter levels. FLX increased the expression of miRNAs as part of the antidepressant effect. It also regulates both neuroinflammation and serotoninergic neurotransmission through miRNAs, such as the miR-16.

Depression and Pain: Use of Antidepressants.

BACKGROUND: Emotional disorders are common comorbid affectations that exacerbate the severity and persistence of chronic pain. Specifically, depressive symptoms can lead to an excessive duration and intensity of pain. Clinical and preclinical studies have been focused on the underlying mechanisms of chronic pain and depression comorbidity and the use of antidepressants to reduce pain. AIM: This review provides an overview of the comorbid relationship of chronic pain and depression, the clinical and pre-clinical studies performed on the neurobiological aspects of pain and depression, and the use of antidepressants as analgesics. METHODS: A systematic search of literature databases was conducted according to pre-defined criteria. The authors independently conducted a focused analysis of the full-text articles. RESULTS: Studies suggest that pain and depression are highly intertwined and may co-exacerbate physical and psychological symptoms. One important biochemical basis for pain and depression focuses on the serotonergic and norepinephrine system, which have been shown to play an important role in this comorbidity. Brain structures that codify pain are also involved in mood. It is evident that using serotonergic and norepinephrine antidepressants are strategies commonly employed to mitigate pain Conclusion: Literature indicates that pain and depression impact each other and play a prominent role in the development and maintenance of other chronic symptoms. Antidepressants continue to be a major therapeutic tool for managing chronic pain. Tricyclic antidepressants (TCAs) are more effective in reducing pain than Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin- Noradrenaline Reuptake Inhibitors (SNRIs).