Beneficial effect of aspirin against interferon‐α‐2b—induced depressive behavior in Sprague Dawley rats

Abstract

Accumulating data advocates that inflammatory mediators may contribute to depression in experimental models as well as in humans. Nonetheless, whether anti-inflammatory treatments can prevent depression still remains controversial. To substantiate our hypothesis, we used an interferon-α-2b model of depression using Sprague Dawley rats. Interferon-α-2b is a cytokine which activates immune response and also produces depression. The animals were treated for 21 days with aspirin (10 mg/kg, per oral (p.o.)) dexamethasone (1 mg/kg p.o.) and amitriptyline (10 mg/kg p.o.). Amitriptyline was used as reference standard, and given concurrently with aspirin and dexamethasone to examine any synergy. Interferon-α-2b (6000 IU/kg, intraperitoneal (i.p.)) was administered in all the above groups daily, except normal control. Tests performed included sucrose preference test, behavioural tests like forced swim test, elevated plus maze, light dark box and locomotor activity along with biochemical estimations like serum cortisol and brain neurotransmitters. The rats in the group treated with Interferon-α-2b produced depressive behaviour in rats. We found that animals treated with aspirin decreased immobility time in forced swim test, increased sucrose preference, decreased serum cortisol and increased brain serotonin levels signifying antidepressant action. In contrast, there was no effect in groups treated with dexamethasone. Our results suggest that aspirin can serve as a potential antidepressant both individually and as adjuvant agent in the treatment of depression. Inhibition of the cyclo-oxygenase-2 levels and prostaglandins concentration or any other potential physiological and biochemical mechanisms may be involved in antidepressant effect.

Effect of Aspirin vs Placebo on the Prevention of Depression in Older People

“…6 Aspirin was associated with increased sucrose preference and reduced immobility in the forced swim test, as well as decreased cortisol levels and increased brain serotonin levels in an interferon model of depression in Sprague Dawley rats, suggesting both clinical model efficacy and influences on salient pathways. 38 Several pharmacoepidemiology studies suggest that people taking aspirin may have a lower risk for depression, 33,34,39,40 notwithstanding some conflicting data that have failed to show a benefit of aspirin. 41,42 Early clinical trials of aspirin in mood disorders have also generated promising but preliminary signals of efficacy.…”

Visceral Inflammation and Immune Activation Stress the Brain

“…Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) is a PG D 2 receptor that is also involved in the behavioral effects of LPS ( 206 , 207 ). Inhibition of PG synthesis by nonsteroidal antiinflammatory drugs attenuates the sickness and depression-like behavior induced by LPS, Bacille Calmette–Guérin and interferon-α-2b ( 204 , 208 – 211 ). Cyclooxygenase-2 inhibitors, particularly celecoxib, have the potential to ameliorate depression in humans, although a meta-analysis of the pertinent clinical trials points out that the subgroup of patients who could benefit from such therapy has not yet been identified ( 212 ).…”

Do We Build Similar Molecules for Comorbid Diseases? Tevarud in Drug Design, an Analysis for Depression and Inflammation

“…Depression and inflammation, two major diseases that affect millions of people worldwide, have been shown these late years to be connected to each other due to biological, hormonal, or environmental factors. − While on the one hand some studies demonstrated that pro-inflammatory cytokines, markers increased in the case of inflammation, can induce behavioral sicknesses, , on the other hand some depressed patients were found to present high serum levels of pro-inflammatory cytokines . This interconnection has also been suggested during clinical investigations where the antidepressant (AD) activity of some anti-inflammatory (AI) drugs such as acetyl salicylic acid (aspirin) or celecoxib has been revealed. Similarly, some AI properties have also been attributed to desipramine and fluoxetine, two widely used AD molecules …”