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Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been implicated in mood and anxiety disorders and is upregulated by antidepressants. It has marked effects on synaptic and extra-synaptic plasticity through tropomyosin receptor kinase B (TrkB). Importantly, early life stressors that affect BDNF production are known to predispose individuals towards the later development of depression or anxiety disorders. Yet, few studies have actually assessed the long-term impact of selective early life BDNF manipulation. Therefore, we utilized a knock-in transgenic mouse line (TrkB F616A ) with a mutation on the full-length TrkB receptor (TrkB.tk+), to reversibly block early postnatal BDNF/TrkB signaling. This was done during exposure to early life stress (maternal separation) followed by exposure to 35 days of chronic unpredictable stress (CUS) in adulthood. The TrkB.tk + mice that received the stressor treatments displayed a blunted anhedonic-like response (sucrose preference), compared to stressed animals that did not have the transient early life TrkB knockdown. But the TrkB.tk + mice actually showed an enhanced anxiety-like response in an open field in response following the CUS. This was paralleled by reductions of BDNF within the PFC and hippocampus of stressed TrkB.tk + mice, but basal elevations of BDNF was evident in the nucleus accumbens. These data are consistent with the contention that early in life, BDNF may program stress responsive circuits but this may differentially map onto depressive and anxiety-like responses in adulthood., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Considerable recent attention has focused on the rapid antidepressant effects observed in treatment resistant patients produced by the NMDA receptor antagonist, ketamine. Surprisingly, the effects of ketamine in the context of stressor exposure, as well as the consequences of its chronic use are unclear. Thus, we assessed the impact of acute and repeated ketamine treatment together with acute [restraint or lipopolysaccharide (LPS)] or chronic (unpredictable different psychogenic challenges) stressor exposure. Importantly, acute ketamine treatment did provoke an antidepressant-like effect in a forced swim test (FST) and this effect lasted for 8 days following repeated exposure to the drug. Although acute restraint and LPS individually provoked the expected elevation of plasma corticosterone and brain-region specific monoamine variations, ketamine had no influence on corticosterone and had, at best, sparse effects on the monoamine changes. Similarly, ketamine did not appreciably influence the stressor induced neurochemical and sucrose preference alterations, it did however, dose-dependently reverse the LPS induced elevation of the pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Likewise, repeated ketamine administration increased adult hippocampal neurogenesis. These data indicate that repeated ketamine administration had greater behavioral consequences than acute treatment and that the drug might be imparting antidepressant effects through its effects on neuroplasticity and inflammatory processes rather than the typical neurochemical/hormonal factors affected by stressors. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'., (Copyright © 2016 Elsevier Ltd. All rights reserved.)