Beneficial effect of fluoxetine treatment aganist psychological stress is mediated by increasing BDNF expression in selected brain areas

Abstract

SSRI antidepressant fluoxetine is widely used to treat psychological stress related disorders, however the underlying working mechanisms is not fully understood, as SSRIs can rapidly increase the extracellular serotonin levels but it normally takes weeks to reveal their therapeutic effect in the stress-related psychological disorders. Our previous study demonstrated that purely psychological stress without any physic stimuli induces a biphasic change in the expression of brain-derived neurotrophic factor (BDNF), which immediately decrease and then gradually increase after the stress; and that the latter BDNF increase in response to the psychological stress involves the activation of serotonin system. To investigate the role of BDNF in the fluoxetine treatment for stress-related psychological disorders, we examined the mRNA and protein levels of BDNF in the brain of Sprague-Dawley (SD) rats, which were pretreated with fluoxetine at 10 mg/kg or vehicle solution for 14 days, over 24 hour after an acute psychological stress exposure. In situ hybridization and immunohistochemistry were performed to detect the expression of BDNF at different time points in various brain regions after the psychological stress. We found that fluoxetine treatment completely blocked the BDNF decrease induced by the psychological stress, and also enhanced the gradual increase in the expression of BDNF in most of the brain regions except VTA after the psychological stress. The results suggest that the enhancement in BDNF levels induced by chronic fluoxetine treatment mediates the therapeutic effect against psychological stress.

Achyranthes aspera ameliorates stress induced depression in mice by regulating neuroinflammatory cytokines

“… 44 Importantly, it is worth to note that several drugs exerts their antidepressant effect by increasing BDNF levels within hippocampal and PFC. 46 , 47 , 48 The results observed in the present investigation support this notion. Chronic A. aspera treatment restores BDNF level in hippocampus and PFC reduced by chronic stress exposure .…”

Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents

“…The data that were reviewed herein implicate BDNF in the antidepressant-like effects of flavonoids. This mechanism of action is relevant because it has been associated with the actions of clinically effective antidepressant drugs [ 80 , 120 ]. BDNF modulates neurotransmitters and receptor activity and is involved in the activation of serotonergic, noradrenergic, and dopaminergic pathways and neurogenesis in the hippocampus and cerebral cortex, which are implicated in the neurobiology of psychiatric disorders, including depression.…”

Novel rapid-acting antidepressants: molecular and cellular signaling mechanisms

“…In mice that have been genetically modified to express a mutated form of BDNF that impairs its expression, the antidepressant effects of both ketamine [ 47 ] and fluoxetine [ 48 ], an SSRI, are blocked. The difference is the mechanism by which these agents influence BDNF: typical antidepressant agents increase the expression but not the release of BDNF, and this occurs only after chronic administration of at least 2 weeks [ 49 , 50 ]; ketamine causes rapid, activity-dependent release of BDNF [ 27 ] as well as increased expression of BDNF [ 31 ] after a single dose.…”