Abstract
Adolescence is characterized as a period of increased social behavior, risk taking, and novelty seeking, partly due to ongoing maturation in critical brain areas and the hypothalamic-pituitary-adrenal (HPA) negative-feedback system. During this period there is heightened vulnerability to stress that can drive neuro-immune-endocrine remodeling, resulting in the emergence of maladaptive behaviors that increase susceptibility to alcohol and substance abuse. Here we used a rat model to investigate the impact of chronic adolescent unpredictable stress on a battery of behavioral measures to assess anxiety, novelty seeking, risk taking, depression, and voluntary ethanol consumption while determining whether the PPARγ agonist rosiglitazone can attenuate these effects. Adolescent female rats that experienced stress showed increased risk taking behavior and novelty seeking behavior with no change in ethanol consumption. The administration of rosiglitazone during stress induction attenuated stress-induced cortisol elevation, normalized risk taking behavior in a model anxiety, and attenuated novelty seeking in a task-specific manner. Depressive-like behavior was not impacted by adolescent unpredictable stress or the administration of rosiglitazone. The results from this study demonstrate that exposure to unpredictable stress during adolescence increases the prevalence of maladaptive behaviors that are known to increase susceptibility to alcohol and substance abuse, and that rosiglitazone may be an effective therapeutic to attenuate the emergence of select risk taking and novelty seeking behaviors in females.
Highlights
Adolescence is characterized as a period of increased social behavior, risk taking, and novelty seeking in both humans and rodents (Spear, 2000)
By administering rosiglitazone during adolescent chronic unpredictable stress, we reveal task-specific attenuation of stress-induced behaviors following a battery of tests to assess anxiety, novelty seeking, depression, ethanol consumption, and risk taking behavior that may contribute to increased vulnerability to substance use disorder and the emergence of other maladaptive behaviors
The aims of this study were to investigate the effects of chronic unpredictable stress during adolescence on anxiety, FIGURE 8 | Novelty seeking: Novel object recognition (NOR)
Summary
Adolescence is characterized as a period of increased social behavior, risk taking, and novelty seeking in both humans and rodents (Spear, 2000). The development of stress-induced maladaptive behaviors can result in the emergence of alcohol and substance abuse, compulsive gambling, and generalized risk taking behavior (Sinha, 2008; Carroll et al, 2017; Teixeira et al, 2017; Duffy et al, 2018; Horak et al, 2021). These data suggest that uncontrolled exposure to stressors during this period of heightened neuronal plasticity may act as an important trigger for neuronal circuit remodeling that persists into adulthood
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