Cetamina melhora alteração comportamental depressiva símile induzida pela administração crônica de dexametasona em ratos

Abstract

Depression is an illness that affects thousands of individuals worldwide, impairing both emotional and functional capacities of the patient, while also interfering with the social, economic, and occupational aspects of their lives. Moreover, challenges exist regarding the pharmacological treatment of depression, such as drug resistance and delayed therapeutic onset, characterized by low adherence to conventional antidepressant medications, not to mention potential side effects caused by them. Consequently, the development of methods to analyze the disease and, concurrently, its medications and treatments became necessary. From this need, scientific and pharmacological knowledge has evolved, leading to the discovery and production of new drugs aimed at combating this disorder. Ketamine is a dissociative anesthetic and N-methyl-D-aspartate receptor antagonist, showing promise as a therapeutic option in the treatment of severe depression, with a rapid and sustained onset of antidepressant action from a single administration. With this in mind, the present study aimed to investigate the antidepressant action of ketamine on the behavior of a dexamethasoneinduced depression model in rats. Adult male Wistar rats weighing between 250 and 350g were administered subcutaneous saline (SS), dexamethasone (DEX) at 1.5mg/kg with or without subcutaneous ketamine (KET) at 10mg/kg, and intraperitoneal ketamine (KET) at 10mg/kg. Each group consisted of (n=7-17) rats. On the 14th day of treatment, 2 hours after the administration of specific medications for each experimental group, the rats underwent the Open Field Test (OFT) and Forced Swim Test (FST), respectively. In the Open Field Test, no change in locomotor activity was observed in the animals. However, in the Forced Swim Test, a reversal of the depressant effects of DEX by KET was observed, such as a reduction in immobility time and an increase in climbing time, revealing antidepressant effects. In conclusion, acute administration of subanesthetic ketamine did not alter locomotor activity and demonstrated rapid antidepressant effects in the Forced Swim Test in the DEX-induced depression model.