Intrahippocampal injection of brain-derived neurotrophic factor increases anxiety-related, but not panic-related defensive responses

Abstract

Changes in brain-derived neurotrophic factor (BDNF)-mediated signaling in the hippocampus have been implicated in the etiology of depression and in the mode of action of antidepressant drugs. There is also evidence from animal studies to suggest that BDNF-induced changes in the hippocampus may play a role in another stress-related pathology: anxiety. However, it is still unknown whether this neurotrophin plays a differential role in defensive responses associated with distinguished subtypes of anxiety disorders found in the clinic, such as generalized anxiety and panic disorder. In the present study, we investigated the effect of an acute BDNF injection into the rat dorsal hippocampus (DH) on inhibitory avoidance acquisition and escape expression measured in the elevated T-maze (ETM). We also assessed whether serotonergic neurotransmission may account for such effects. Intra-DH BDNF injection (200 pg) facilitated inhibitory avoidance in ETM. BDNF was equally anxiogenic in the light/dark transition test. Preadministration of the 5-HT1A receptor antagonist WAY-100635 fully counteracted the anxiogenic effect of BDNF in both tests. Intra-DH midazolam administration (10 nmol) impaired avoidance acquisition in ETM, suggesting an anxiolytic effect. Therefore, in the DH, facilitation of BDNF signaling seems to enhance 5-HT1A receptor-mediated neurotransmission to exert an anxiogenic effect associated with generalized anxiety.

How cigarette smoking may increase the risk of anxiety symptoms and anxiety disorders: a critical review of biological pathways

“…Intrahippocampal injections of BDNF in rats lead to an increase in anxiety assessed by facilitatory avoidance and the light-dark test. This was blocked by a 5HT1a antagonist suggesting a modulatory role of serotonin (Casarotto et al 2012). Social deprivation stress leads to the development of anxiety in mice, and this appears to be modulated by reductions in BDNF (Berry et al 2012).…”

“…This was blocked by a 5HT1a antagonist suggesting a modulatory role of serotonin (Casarotto et al. ). Social deprivation stress leads to the development of anxiety in mice, and this appears to be modulated by reductions in BDNF (Berry et al.…”

The Met allele of BDNF Val66Met polymorphism is associated with increased BDNF levels in generalized anxiety disorder

“…On the basis of animal studies, the increase in BDNF levels is implicated in emotional and fear memory formation and consolidation through increased BDNF gene expression and activation of its high-affinity TrkB receptor in the amygdala, hippocampus, and prefrontal cortex (Takei et al, 2011). BDNF-induced changes in the hippocampus may also play a role in stress-related pathology as BDNF infusion in the hippocampus leads to an anxiogenic effect in rats by enhancing the serotonergic signaling mediated by 5-HT1A receptors (Casarotto et al, 2012). Therefore, although the Met variant has been hypothesized to decrease the activitydependent BDNF secretion, but not the constitutive one, the upregulation of peripheral BDNF concentrations in the Met allele carriers might compensate a defective intracellular protein signaling (Egan et al, 2003).…”

Oxidative Imbalance and Anxiety Disorders

“…Intrahippocampal injection of BDNF is able to induce an anxiogenic-like activity [170, 171]. In this context, Dalle Molle and colleagues [172] used a translational approach, using both an animal model and studies in humans, and demonstrated that variations in maternal care (which was related to maternal overprotection) are associated with anxiety and increased peripheral BDNF in both rats and humans [172].…”