Estudo eletroencefalográfico e comportamental da cetamina em um modelo de depressão-símile induzido por dexametasona em ratos

Abstract

Major Depressive Disorder (MDD) is a disease with a highly debilitating nature, characterized by considerable effects on mood and behavior. Antidepressants currently available in clinical practice are associated with several limitations, including late therapeutic initiation. The glutamatergic system is related to the pathophysiology of MDD, so N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine (KET) represent a new therapeutic option due to its rapid onset of action. Thus, the aim of the present study was to study the acute antidepressant effects of ketamine on behavior and electroencephalogram in a dexamethasone-induced model of depression in rats. Adult male Wistar rats weighing 250-350g were used. These animals were treated with saline (SS) subcutaneously (SC), KET (10 mg/kg intraperitoneally, IP) associated or not with DEX (16 μg/kg, SC). Animals were treated for 21 days with SS and DEX. On the last day, 30 minutes after SS and DEX administration, KET was administered. After 30 minutes, the electroencephalographic records (for 20 minutes) were initiated and the behavioral tests were performed [(Open Field Test (OFT) and Forced Swim Test (FST)]. In the analyzed parameter of the center/periphery time ratio, it was observed that ketamine, in the SS+KET and DEX+KET groups, significantly reduced this parameter, showing an antidepressant/anxiolytic effect. In FST, KET reduced the immobility time and increased the climbing time, demonstrating antidepressant effect. However, this effect of KET was reversed by the association with DEX (DEX+KET). In the analysis of electroencephalogram (EEG) results, it was observed that the administration of KET increased the power of alpha and beta high brain waves, evidencing the antidepressant effect of KET on the EEG. The acute administration of ketamine showed antidepressant/anxiolytic effects related to increase in the average spectral power of the alpha and beta high brain bands.