Venlafaxine and Nortriptyline Reverse Acute Dexamethasone-Induced Depressive-Like Behaviors in Male and Female Mice

Major depression can be triggered by stressful events that promote deregulation of the hypothalamic-pituitary-adrenal axis response and, in some circumstances, persistent elevation of circulating glucocorticoid levels. Animal models are widely used to investigate the mechanisms responsible for the etiology and treatment of major depression. However, to mimic the dysfunction of the hypothalamic-pituitary-adrenal axis in rodents, animals should be exposed to sustained physical and psychological stressful situations. These animal models of depression are labor intensive and impact individual animals differently. Aiming to add evidence for a new acute neuroendocrine model of depression, male and female mice were treated with a single administration of dexamethasone, and behavioral effects were evaluated in the presence and absence of the antidepressants nortriptyline and venlafaxine. Male and female Swiss mice were treated with dexamethasone (0.07 mg/kg, subcutaneously) and the mouse behavior was assessed in the tail suspension and open field tests at 4 h, 24 h, and 7 days after administration. Dexamethasone induced depressogenic-like states in both sexes at 4 and 24 h after injection. Additionally, acute dexamethasone increased latency to body fur licking, thus corroborating the depressive-like behavior. The treatment with nortriptyline and venlafaxine (both at 30 mg/kg, intraperitoneally) blocked dexamethasone-induced increase in the immobility time and the latency to self-care. In conclusion, the present findings suggest that a single administration of dexamethasone induces depressive-like states in male and female mice, and these behavioral alterations are counteracted by conventional antidepressants. Ultimately, these data provide new evidence for an acute neuroendocrine model of depression. Public Health Significance Depression causes a significant impact in the public health. Innovative treatments are needed and rodents are widely used to search for new antidepressants. However, it is labor intensive to induce a depressive state in rodents. This study provides an innovative acute way of inducing a depressive state in mice. Our findings showed that a single administration of dexamethasone promotes a depressive state in male and female mice, which is blocked by conventional antidepressants.