Bases moleculares subyacentes al efecto de fluoxetina sobre la expresión conductual de la memoria en un modelo de depresión animal

Abstract

Affective disorders, including anxiety and depression, are nowadays part of the main threats in public health. Among the most commonly used drugs for the treatment of depression is fluoxetine. However, there are controversial results regarding its side effects, since some authors have shown that these drugs induce a deleterious effect on memory, while others suggest that they improve cognitive function.

The objective of this study was to assess the effects of chronic administration of fluoxetine (10 mg / kg / day) on memory formation processes in Swiss albino mice (N: NIH) with bilateral olfactory bulbectomy compared to mice without extraction of olfactory bulbs (Sham, controls), N = 10 - 14. Memory performance was assessed on day 27 of treatment in the object recognition test (ORT). Subsequently, the level of nitric oxide (NO) in the hippocampus was quantified by Griess technique. In addition, the antidepressant effect in the open field tests (TCA) and tail suspension (TSC) was evaluated. The data were analyzed by two-way ANOVA followed by an LSD test.

The results show that chronic treatment with fluoxetine in Sham animals decreased the percentage of exploration time of the new object in ORT, which is interpreted as a memory deficit (p≤0.05). A similar deleterious effect was observed in bulbectomized animals (BO) administered with saline solution, which was reversed by chronic fluoxetine treatment (p≤0.05). Sham animals that received fluoxetine showed lower concentrations of NO than Sham-saline animals (p≤0.05), while BO-fluoxetine animals had NO concentrations almost double compared to BO-saline (p≤ 0.05). The antidepressant managed to reverse the immobility behavior shown by BO animals in the TSC and hyperlocomotion in TCA (p≤0.05).

Finally, the present work provides new evidence about the effects of fluoxetine on the processes of memory formation in an animal model of depression, indicating that the effects are dependent on the baseline condition of the animal