Venlafaxine restores memory impairment in an animal model of depression.

BIANCONI SANTIAGO; MARIA BELEN PORETTI; GASPARINI GATICA MAURO; CARLINI, VALERIA PAOLA

Congreso; Reunión Anual de la Sociedad de Biociencia; 2020

Background: major depressive disorder is a prevalent, chronic, disabling, and multidimensional mental illness. Cognitive dysfunction represents a core diagnostic and symptomatic criterion of MDD, and is a principal determinant of functional non-recovery. Venlafaxine (VEN), a serotonin-norepinephrine reuptake inhibitor (SNRI), is an antidepressant drug commonly used to treat a wide spectrum of mood disorders including treatment-resistant depression. Despite decades of clinical use, the impact of VEN on memory processes is still incompletely understood. Objectives: in the present study we investigated VEN effect on memory and nitric oxide (NO) level in the hippocampus in an animal model of depression (olfactory bulbectomy). Material and methods: thirty-two adult male albino Swiss mice were divided into sham and olfactory bulbectomized (OB) groups, and orally treated during 28 days with saline (S) or VEN (10 mg/kg/day). The last day of treatment, the tail suspension test (TST) was performed and then, long-term memory retention was evaluated using the object recognition test (ORT). After that, animals were euthanized and their hippocampi dissected to determine NO levels by Griess. Statistics: two-way ANOVA test followed by LSD post hoc test whenever appropriate. Results: sham-VEN and OB-S animals showed a memory impairment compared with sham-S animals (F(1,31)= 12.46, p≤0.05), and OB-VEN animals exhibited enhanced memory performance in ORT compared to OB-S (p≤0.05). Furthermore, a significant reduction in NO levels was detected in OB-S but VEN treatment reversed this effect in OB group (OB-S 1.25 nmol/µg protein vs. OB-V 3.79 nmol/µg protein). These results suggest that VEN counteracts memory impairment in OB animals with participation of the NO pathway. To improve the diagnosis and treatment of depression and its associated cognitive impairments, a better understanding of the neuropathophysiological basis of this disabling illness is required.