Social and non-social anxiety in adolescent and adult rats after repeated restraint

Abstract

Adolescence is associated with potentially stressful challenges, and adolescents may differ from adults in their stress responsivity. To investigate possible age-related differences in stress responsiveness, the consequences of repeated restraint stress (90 min/day for 5 days) on anxiety, as indexed using the elevated plus-maze (EPM) and modified social interaction (SI) tests, were assessed in adolescent and adult Sprague-Dawley male and female rats. Control groups at each age included non-stressed and socially deprived animals, with plasma corticosterone (CORT) levels also measured in another group of rats on days 1 and 5 of stress (sampled 0, 30, 60, 90, and 120 min following restraint onset). While repeatedly restrained animals exhibited similar anxiety levels compared to non-stressed controls in the EPM, restraint stress increased anxiety at both ages in the SI test (as indexed by reduced social investigation and social preference). Daily weight gain measurements, however, revealed more marked stress-related suppression of body weight in adolescents versus adults. Analysis of stress-induced increases in CORT likewise showed that adolescents demonstrated less habituation than adults, embedded within typical sex differences in CORT magnitude (females greater than males) and age differences in CORT recovery (adolescents slower than adults). Despite no observable age-related differences in the behavioral response to restraint, adolescents were more sensitive to the repeated stressor in terms of physiological indices of attenuated weight gain and habituation of stress-induced CORT.

Figure 1

The effects of repeated (5 days) restraint stress (RS) or social deprivation (SD) on (a) percent open arm entries and (b) percent open arm time in both adolescent and adult male and female rats tested for 5 min in the elevated plus-maze. Asterisks (*) indicate a significant difference from non-manipulated (NM) control animals, with p ≤ .05. In this figure (and in all subsequent figures) bars depict the mean for a particular group, while vertical lines represent the standard error of the mean.

Figure 2

The effects of repeated restraint stress (RS) or social deprivation (SD) on (a) percent protected head-dips and (b) percent protected stretched attend postures in both adolescent and adult male and female rats tested for 5 min in the elevated plus-maze. Asterisks (*) indicate a significant difference from non-manipulated (NM) control animals with p ≤ .05.

Figure 3

The effects or repeated restraint stress (RS) or social deprivation (SD) on (a) social investigation and (b) social preference/avoidance in both adolescent and adult male and female rats during a 10-min social interaction test. Asterisks (*) represent a significant difference from non-manipulated controls with p ≤ .05.

Figure 4

The effects of repeated restraint stress (RS) or social deprivation (SD) on (a) play behavior and (b) number of crossovers in both adolescent and adult male and female rats during a 10-min social interaction test. Asterisks (*) depict a significant differences from non-manipulated (NM) control animals with p ≤ .05.

Figure 5

The corticosterone response to acute (day 1) and repeated (day 5) restraint stress for both male and female adolescent and adult rats at 15, 30, 60, or 120 min after onset of the 90-min stressor. Baseline measurements (0 min assessments) were collected in a separate group of animals taken directly from the home cage. Dark (filled) symbols represent stress-induced elevations in corticosterone on the first day of stressor exposures, while light (open) symbols show the corticosterone response on the last (5^th) day or stressor exposure. The same animals were sampled at a given time point on day 1 and day 5, with different animals sampled at each post-onset interval. Since the baseline data were uniformly low and did not differ across groups, data were not adjusted for these baselines.