Dorsal Hippocampus ERK2 Signaling Mediates Anxiolytic-Related Behavior in Male Rats

Abstract

Background: Anxiety disorders are the most common neuropathologies worldwide, but the precise neuronal mechanisms that underlie these disorders remain unknown. The hippocampus plays a role in mediating anxiety-related responses, which can be modeled in rodents using behavioral assays, such as the elevated plus maze. Yet, the molecular markers that underlie affect-related behavior on the elevated plus maze are not well understood. Methods: We used herpes simplex virus vector delivery to overexpress extracellular signal-regulated kinase-2, a signaling molecule known to be involved in depression and anxiety, within the dorsal hippocampus of adult Sprague-Dawley male rats. Three days post virus delivery, we assessed anxiety-like responses on the elevated plus maze or general locomotor activity on the open field test. Results: When compared to controls, rats overexpressing extracellular signal-regulated kinase-2 in the dorsal hippocampus displayed an anxiolytic-like phenotype, per increases in time spent in the open arms, and less time in the closed arms, of the elevated plus maze. Furthermore, no changes in locomotor activity as a function of virus infusion were observed on the open field test between the experimental groups. Conclusion: This investigation demonstrates that virus-mediated increases of extracellular signal-regulated kinase-2 signaling, within the hippocampus, plays a critical role in decreasing anxiogenic responses on the rat elevated plus maze. As such, our data provide construct validity, at least in part, to the molecular mechanisms that mediate anxiolytic-like behavior in rodent models for the study of anxiety.

Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury

“…However, six days post-SNL, anxiety- and depression-like behaviors were not completely developed even if SNL-induced aversion was detected ( Suzuki et al, 2007 ; Wu et al, 2019 ). However, the evidence demonstrated that the analyzed anxiety- and depression-related DEGs such as Gria1 ( Rivera et al, 2020 ), Mapk1 ( Sierra-Fonseca et al, 2019 ), Mapk9 ( Thomson et al, 2020 ), and Fkbp5 ( Zannas et al, 2019 ) contributed to anxiety or depression symptoms in rodents. The further study on the gene expression profiles and emotion-related behaviors including anxiety- and depression-like behaviors at the later stage of neuropathic pain should be carried out.…”

CGRP causes anxiety via HP1γ–KLF11–MAOB pathway and dopamine in the dorsal hippocampus

“…It has been suggested that the various hippocampal regions subserve distinct functions, with the dorsal hippocampus involved in memory, learning and spatial learning, while the ventral hippocampus cooperates with the amygdala to regulate anxiety-related behavior 28 – 30 . More recently, it was shown that the dorsal CA1 subregion of the hippocampus is activated by an anxiogenic environment 31 and that genetic manipulation of the dorsal hippocampus has an anxiogenic effect 32 , 33 . Thus, the dorsal hippocampus plays a critical role in the regulation of anxiety behavior.…”

Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood

“…5 B, 6 B); highlighting a long-term FLX-induced molecular signature between the sexes that results in anxiety-like behavior in both females and males. Subsequently, we also evaluated intracellular hippocampal and prefrontal cortex ERK-CREB-BDNF signaling markers, given that these downstream molecules also modulate affect-related behavior in intact adult rodents 25 , 30 , 48 . Here, we found that juvenile FLX pretreatment resulted in a long-term decrease in the phosphorylation of ERK2 and CREB within both brain regions (Fig.…”

“…This is a classic task used to evaluate anxiety-like behavior in rodents 25 , 37 , 79 . Briefly, the animals were tested in a plus-shaped maze (under red light conditions; ~ 30 lx) that was elevated 50 cm from the floor.…”