Adolescent Development Determines the Effects of Agonistic Social Stress on Rat Behavior and Locus Coeruleus Physiology

Stress is a causal factor in the development of many psychological disorders such as depression, anxiety, drug addiction, and conduct disorder. The degree to which stress affects the development of these disorders depends on several factors including the nature of the stressor, it’s timing with respect to critical periods in brain development, and genetic predispositions towards resilience or vulnerability. Adolescence is a period of development during which stress can have an enduring impact on behavior and susceptibility for affective disorders. The experiments in this thesis used the rat resident-intruder stress to model the interaction between adolescent development and the consequences of social stress on behavior and brain physiology. Rats representing 3 stages of adolescent development, early adolescent (EA, p28-p35), Mid-adolescent (MA, p42-p49) and adult (p63-p70), were placed in the cages of aggressive Long-Evans retired breeder rats daily for 7 days and tested in behavioral models of affective disorders 24-72h later. In EA rats selectively, social stress increased active coping behaviors in the defensive burying and forced swim tests. Because the locus coeruleus (LC)-norepinephrine system has been implicated in these active behaviors, LC neuronal activity was also quantified. Socially stressed EA rats had elevated LC spontaneous discharge rates and diminished phasic responses to sensory stimuli compared to controls, similar to the effects produced by the stress-related neuropeptide, corticotropin-releasing factor (CRF). Moreover, microinjection of a CRF antagonist into the LC selectively inhibited neurons of stressed EA rats, suggesting that exposure to social stress during early adolescence induces tonic CRF release onto LC neurons, shifting the mode of discharge to a high tonic state that may promote active coping. Interestingly, opposing behavioral and neuronal consequences were seen in adults as well as in EA rats exposed to social stress but tested in adulthood. Taken together, these results demonstrate that social stress interacts with adolescent development to alter coping strategies to novel challenges, with both immediate and long-lasting effects. The data also reinforce the fact that adolescence is physiologically and behaviorally distinct from adulthood and that treatments for stress-induced psychopathologies should reflect those differences