Behavioral inhibition and glucocorticoid dynamics in a rodent model

Abstract

Behavioral inhibition (i.e. avoidance of unfamiliar) has been linked to significant differences in stress physiology and health. Developing an animal model of this common temperament provides a means to experimentally study the development and physiology of this trait as it relates to stress-related health processes. To elaborate such an animal model, we studied individual rat responses to two novel situations that mimic behavioral inhibition tests for humans (one non-social and one social). We measured individual consistency of behavioral responses across tests and time, and examined the relationship between behavior and glucocorticoid levels in outbred Sprague-Dawley male rats. Individuals were consistent in their behavioral responses to the same novel environment over time, but not in their responses across two different environments (i.e. non-social vs. social). A third of males were slow to approach novelty in both arenas (INHIBITED) and another third were fast to approach in both arenas (NON-INHIBITED). Behavioral inhibition was relatively stable across time and was associated with increased glucocorticoid production at baseline and in response to novelty but not during a post-novelty recovery period. Glucocorticoid levels were more closely related to their responses to the social novel arena than the non-social arena. Thus, behavioral inhibition is associated with acute and basal glucocorticoid over production and social inhibition is a more important predictor of adrenal activity than non-social inhibition. These preliminary observations provide strong support for an animal model of human behavioral inhibition and identify specific aspect of glucocorticoid production dynamics to examine in behaviorally inhibited children. Keywords behavioral inhibition; neophobia; exploration; glucocorticoid profiles; individual differences; stress In the United States, approximately 20% of children tested show stable signs of behavioral inhibition or shyness -a behavioral predisposition that indicates fear of the unfamiliar and avoidance of novelty in different situations [1][2]. In children, this trait is relatively stable over time, with 60% of shy 1-year-olds remaining inhibited 4 years later [3]. These children are also more prone to certain behavioral and health problems, including increased risk for drug use in boys [4], problem behavior [5], anxiety disorders [2,6-8] and allergies [9]. One physiological trait associated with inhibition that may explain certain behavioral and health trajectories is a greater release of glucocorticoids from the hypothalamic-pituitary-adrenal (HPA) axis during unstimulated and stimulated periods [3,[10][11][12][13]. Given the complex relationships between

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

“…These characteristics resemble a behavioral inhibition profile that has been linked to significant differences in stress physiology and is associated with acute and basal glucocorticoid overproduction (Cavigelli et al, 2007). These findings suggest that the interaction between high anxiety and low exploration traits represent a higher risk to the effects of stress in congruence with the human traits of neuroticism and extraversion, which have been suggested to be predictors of an individual's vulnerability or resilience to develop depression (Lara and Akiskal, 2006).…”

Within‐litter variance in early rat pup–mother interactions and adult offspring responses to novelty

“…In adulthood (PND 68-82), we tested offspring responses to two novel arenas that were designed to reduce anxietyprovoking stimuli such as white light and open space (Cavigelli et al, 2007). The arenas are 120 cm  120 cm with 46-cm high white polypropylene walls and a clear plastic cover.…”

Temperament moderates the influence of periadolescent social experience on behavior and adrenocortical activity in adult male rats

“…Previously we found that rat (Sprague-Dawley) neophobia/philia, characterized by locomotion in an unfamiliar and protected arena, was related to latency to approach novelty, and was moderately stable from pre-weaning age throughout adulthood, and was reproducible across studies (Cavigelli & McClintock, 2003; Cavigelli et al, 2007; Cavigelli, Ragan, Michael, Kovacsics, & Bruscke, 2009). Neophobic or inhibited males also had greater plasma CORT responses to novelty and stress compared with neophilic or non-inhibited males (Takahashi, 1992; Cavigelli & McClintock, 2003; Veenema, Sijtsma, Koolhaas, & de Kloet, 2005; Cavigelli et al, 2007; Qi et al, 2010; Díaz-Morán et al 2013; c.f.…”

“…Neophobic or inhibited males also had greater plasma CORT responses to novelty and stress compared with neophilic or non-inhibited males (Takahashi, 1992; Cavigelli & McClintock, 2003; Veenema, Sijtsma, Koolhaas, & de Kloet, 2005; Cavigelli et al, 2007; Qi et al, 2010; Díaz-Morán et al 2013; c.f. Dellu et al 1996).…”

“…Behavioral inhibition (BI) or neophobia is a relatively stable behavioral trait in humans and rodents that emerges early in development (infancy) and is characterized by fear and avoidance of novel or unfamiliar situations and objects, and heightened cortisol reactivity after exposure to psychosocial stress, novel social situations, and novel objects (Kagan, Reznick, & Snidman, 1987; Schmidt et al, 1997; Cavigelli & McClintock, 2003; Cavigelli et al, 2007; Walker & Mason 2012). In humans, this trait has been associated with increased risk of adolescent and adult mood disorders, which are often associated with altered adrenocortical regulation (e.g.…”