Safety signals are learned cues that predict stress-free periods whereas behavioral control is the ability to modify a stressor by behavioral actions. Both serve to attenuate the effects of stressors such as uncontrollable shocks. Internal and external cues produced by a controlling behavior are followed by a stressor-free interval, and so it is possible that safety learning is fundamental to the effect of control. If this is the case then behavioral control and safety should recruit the same neural machinery. Interestingly, safety signals that prevented a behavioral outcome of stressor exposure that is also blocked by control (reduced social exploration) failed to inhibit activity in the dorsal raphé nucleus or use the ventromedial prefrontal cortex, the mechanisms by which behavioral control operates. However, bilateral lesions to a region of posterior insular cortex, termed the "sensory insula," prevented the effect of safety but not of behavioral control, providing a double-dissociation. These results indicate that stressor-modulators can recruit distinct neural circuitry and imply a critical role of the sensory insula in safety learning.

Adolescence is a developmental period in which brain structures involved with stress responses, such as the medial pre-frontal cortex (mPFC), mature. Therefore, exposure to a stressor at this time may have effects that endure the lifespan. The goal of the present study was to determine whether behavioral control over an adolescent stressor mitigates the behavioral and neurochemical consequences of the stressor as occurs in adult rats. Adolescent rats (post natal day 35) were exposed to either inescapable (IS) or escapable tailshocks (ES). As in adults we observed a “stressor controllability effect”; IS reduced social exploration and activated the serotonergic dorsal raphé nucleus while ES did not. Excitotoxic lesions of the medial prefrontal cortex prevented the stressor controllability effect. We also demonstrate that a controllable adolescent stress prevents the behavioral and neurochemical consequences of IS in adulthood. Thus, the controllability of a stressor during adolescence is an important psychological factor.