To Approach or Avoid: An Introductory Overview of the Study of Anxiety Using Rodent Assays

Abstract

Anxiety is a widely studied phenomenon in behavioral neuroscience, but the recent literature lacks an overview of the major conceptual framework underlying anxiety research to introduce young researchers to the field. In this mini-review article, which is aimed toward new undergraduate and graduate students, we discuss how researchers exploit the approach-avoidance conflict, an internal conflict rodents face between exploration of novel environments and avoidance of danger, to inform rodent assays that allow for the measurement of anxiety-related behavior in the laboratory. We review five widely-used rodent anxiety assays, consider the pharmacological validity of these assays, and discuss neural circuits that have recently been shown to modulate anxiety using the assays described. Finally, we offer related lines of inquiry and comment on potential future directions.

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

“…Specifically, when compared to the VEH-pretreated groups, adult female mice with FLX history, spent less time in the center of the OFT and the lighted area of the LDB, while spending more time inside the closed arms of the EPM (see Figs. 2 A, 3 A, 4 A)—a behavioral response that, collectively, indicates that SSRI pretreatment mediates a long-term upward shift in baseline responses to anxiety-relevant situations 37 . Of note, these results agree with previous studies using similar behavioral tasks wherein early-life FLX induced an anxiety-like phenotype in adult male rodents 16 – 19 ; critically, the current work expands these findings to female mice and further explores potential biochemical mechanisms of this effect.…”

“…This behavioral profile, wherein FLX rescues early-life SSRI-induced alterations to anxiety-related situations, has been reported previously in male mice 18 and rats 19 . This emphasizes that early-life antidepressant treatment renders both males and females in need of subsequent antidepressant re-exposure to normalize responses when encountering anxiety-inducing situations 37 , a critical advance considering the prevalence of mood disorders and SSRI prescription amongst females.…”

“…This regimen was chosen because it resembles the timeframe of development for human adolescence 74 . After a 21-day resting period (PD70), separate cohorts of animals were either euthanized (for tissue collection) or tested in behavioral tasks designed to assess anxiety-like behavior 37 , 75 —the open field test (OFT), light/dark box (LDB), and elevated plus maze (EPM). Because adolescent FLX exposure increased reactivity to anxiety-inducing situations in adulthood across all behavioral paradigms (Figs.…”

“…Consequently, young girls are more likely to be prescribed with psychotropic medications like FLX 36 . To address this gap in the literature, the goal of this study is to examine whether juvenile FLX exposure increases reactivity in paradigms commonly used to evaluate anxiety-related behavior 37 in adult female C57BL/6 mice, and if so, whether FLX re-exposure normalizes the SSRI-induced avoidance-like behavioral response. Furthermore, to evaluate the enduring effects of adolescent FLX-pretreatment, and its re-exposure in adulthood, on 5-HTTs and BDNF-related molecules (TrkB, ERK1/2, CREB) within the prefrontal cortex and hippocampus (Fig.…”

Functional disruption of cortical cingulate activity attenuates visceral hypersensitivity and anxiety induced by acute experimental colitis

“…In this assay, the tendency to avoid exploring or running in the open center space (i.e. potentially dangerous) has been validated as a measure of anxiogenic behavior in mice 27 . We observed that after administering CNO, DSS-treated hM4Di-expressing mice spent a significantly greater amount of time exploring the open unprotected center zone compared to DSS-treated mCherry controls (examples in Fig.…”