The antidepressant-like effects of ketamine and fluoxetine in rats exposed to a chronic administration of corticosterone

Abstract

Depression is a common mental disorder. The pathogenesis of depression is intricately tied to the balance and function of monoamine neurotransmitters, as well as the enzymes that degrade these neurotransmitters and the precursors that contribute to their synthesis. One of the issues responsible for the poor success of conventional antidepressant drugs is related to an inadequate understanding of the biology of this disorder. The common feature of current antidepressants is the regulation of monoaminergic neurotransmitter systems. However, ketamine is an anesthetic with dissociative properties that have been shown to improve affective symptoms in patients with refractory depression (10). The purported mechanism of action of ketamine as antidepressant is the antagonism of NMDA glutamate receptors localized to inhibitory GABA interneurons in the brain. In this work we have examined the differences in the antidepressant-like effects between a rapid-acting antidepressant drug (ketamine) and a conventional antidepressant (fluoxetine) in rats exposed to a chronic administration of corticosterone in drinking water. To this end, we conducted different behavioural tests. Our results showed that rats given corticosterone exhibited a depression-like behavior. Ketamine and fluoxetine were able to reduce inmobility induced by corticosterone but didn´t reduce anhedonia. Both drugs showed anxiogenic effects. And both treatments were not able to reverse the anhedonia and anxiety induced by corticosterone.