Behavioral inhibition in rats: a model to examine mechanisms underlying the risk to develop anxiety and depression

Abstract

Behavioral inhibition (BI) is an adaptive defensive response to threat that has been evolutionarily conserved. Extreme BI in childhood is a temperamental disposition for the development of psychopathology. Our goal was to develop a rodent model of BI that is elicited by predator exposure. The ferret exposure test consists of placing a rat in a housing cage in the ferret colony room for 15 min and rating behavior for BI. We show that predator‐induced BI is stable across development when measured in rats (n = 37) in adolescence and again in adulthood (r = 0.475, p < 0.01). BI is reduced by the anxiolytic diazepam (1 mg/kg, 30 min pretreatment; n = 8/group; p < 0.05), and BI is associated with heightened paraventricular nucleus of the hypothalamus (PVN) and CA3 activity as measured by expression of the immediate early gene homer1a (r = 0.379, p < 0.05; r = 0.309, p < 0.05 respectively). Finally, we show that rats with high levels of BI display disruptions in appetitive behavior as a consequence of prior threat exposure compared to rats with low levels of BI (p < 0.001, n = 7 and 8). Taken together, these findings show that rodent BI is a stable, trait‐like characteristic that is associated with maladaptive responding. This model can be useful in identifying the molecular underpinnings for the childhood risk to develop psychiatric illness. This work was supported by NIH grant MH43454, Meriter Hospital and UW HealthEmotions Research Institute.