Ontogeny of fear-, anxiety- and depression-related behavior across adolescence in C57BL/6J mice

Abstract

Adolescence is characterized by behavioral traits such as emotional lability and impulsivity that are associated with increased vulnerability to affective illness and addictions. Research in rodents has found that adolescent rats and mice differ from adults on measures of anxiety-like behavior, noveltyseeking and stress-responsivity. The present study sought to extend these data by evaluating fear-, anxiety-and depression-related behaviors in male C57BL/6J mice aged four (early adolescent), six (peri-adolescent) or eight (early adult) weeks of age. Age-groups were compared on: Pavlovian fear conditioning and extinction, anxiety-like behavior and exploratory locomotion (using elevated plusmaze and novel open field), and depression-related behavior (via forced swim test). Results showed that early adolescent mice exhibited enhanced fear conditioning, but extinguished at a similar rate as adults. There were no major differences in anxiety-like behavior across age-groups, although early adolescent and peri-adolescent mice exhibited less exploratory locomotion than adults. Depressionrelated immobility behavior in the forced swim test was lower in early adolescents than adult mice across three test exposures. Present findings in the C57BL/6J inbred strain add to growing evidence of changes in rodent fear-and stress-related behaviors across the developmental transition from juvenility through adulthood. Understanding the neural basis of these ontogenic changes could provide insight into factors could provide insight into the pathogenesis and treatment of affective disorders that have their origins in adolescence.

Postnatal development of the amygdala: A stereological study in rats

“…Indeed, 50-day-old rats are more attentive and display longer freezing, at a greater distance from the threat, than 20-day-old rats (Bronstein and Hirsch, 1976). In contrast, although 4-week-old mice exhibit more rapid and more robust acquisition of a conditioned association between an auditory stimulus and a foot shock compared with 6-8-week-old mice (Hefner and Holmes, 2007), other studies have shown that 4-week-old mice also display excessive generalization to auditory conditioned stimuli compared with 9-10-week-old mice . Altogether, these observations in mice suggest that aversive associations might be less specific in juveniles than in adults, and, although connectional refinement might occur in the amygdala during this late development , improvement of threat detection and defensive responses might also be linked to the maturation of other brain areas (e.g., prefrontal and sensory cortex) connected to the amygdala.…”

“…Individual components of the fear response are thought to incorporate sequentially as animals mature, eventually giving rise to what are identified as mature fear behaviors (Wiedenmayer, 2009). Indeed, several studies have revealed that distinct fear behaviors emerge at different times during early postnatal life and continue to mature during late postnatal development (Blozovski and Cudennec, 1980;Bronstein and Hirsch, 1976;Chen et al, 2006;Collier et al, 1979;Foster and Burman, 2010;Hefner and Holmes, 2007;Hubbard et al, 2004;Ito et al, 2009;Kim and Richardson, 2007;Moriceau et al, 2004;Raineki et al, 2010;Rudy, 1993;Takahashi, 1992;Wiedenmayer andBarr, 1998, 2001a,b).…”

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

“…The FST was conducted as previously described (Porsolt et al, 1978;Hefner and Holmes, 2007). The apparatus was a transparent Plexiglas cylinder (25 cm high, 20 cm diameter) filled halfway with water (24 ± 11C) into which the mouse was gently lowered for a 10 min trial.…”

Development of Nicotine Loaded Chitosan Nanoparticles for Lung Delivery

“…After inhalation exposure, the first 5 minutes produced highest activity in mice as a result of the fear and stress emotionally from researcher's handling, inhalation device and test process. Hyperactive response induced from stress and fear are consistent with some researchers (Hefner & Holmes, 2007;Strekalova, Spanagel, Dolgov, & Bartsch, 2005 Administration with 50N caused a significant increase (* p<0.05) in the locomotion activity at 15 minutes after inhalation exposure, but no significant differences were observed afterwards. This is mostly possible due to short half-life(t1 2 ⁄ ) of nicotine in mice body.…”