In 1967, Overmier and Seligman found that dogs exposed to inescapable and unavoidable electric shocks in one situation later failed to learn to escape shock in a different situation where escape was possible. Shortly thereafter Seligman and Maier (1967) demonstrated that this effect was caused by the uncontrollability of the original shocks. In this article we review the effects of exposing organisms to aversive events which they cannot control, and we review the explanations which have been offered.There seem to be motivational, cognitive, and emotional effects of uncontrollability. (a) Motivation. Dogs that have been exposed to inescapable shocks do not subsequently initiate escape response in the presence of shock. We review parallel phenomena in cats, fish, rats, and man. Of particular interest is the discussion of learned helplessness in rats and man. Rats are of interest because learned helplessness has been difficult to demonstrate in rats. However, we show that inescapably shocked rats do fail to learn to escape if the escape task is reasonably difficult. With regard to man, we review a variety of studies using inescapable noise and unsolvable problems as agents which produce learned helplessness effects on both instrumental and cognitive tasks, (b) Cognition. We argue that exposure to uncontrollable events interferes with the organism's tendency to perceive contingent relationships between its behavior and outcomes. Here we review a variety of studies showing such a cognitive set. (c) Emotion. We review a variety of experiments which show that uncontrollable aversive events produce greater emotional disruption than do controllable aversive events.We have proposed an explanation for these effects, which we call the learned helplessness hypothesis. It argues that when events are uncontrollable the organism learns that its behavior and outcomes are independent, and that this learning produces the motivational, cognitive, and emotional effects of uncontrollability. We describe the learned helplessness hypothesis and research which supports it.Finally, we describe and discuss in detail alternative hypotheses which have been offered as accounts of the learned helplessness effect. One set of hypotheses argues that organisms learn motor responses during exposure to uncontrollable shock that compete with the response required in the test task. Another explanation holds that uncontrollable shock is a severe stressor and depletes a neurochemical necessary for the mediation of movement. We examine the logical structure of these explanations and present a variety of evidence which bears on them directly.

Dogs which had 1st learned to panel press in a harness in order to escape shock subsequently showed normal acquisition of escape/ avoidance behavior in a shuttle box. In contrast, yoked, inescapable shock in the harness produced profound interference with subsequent escape responding in the shuttle box. Initial experience with escape in the shuttle box led to enhanced panel pressing during inescapable shock in the harness and prevented interference with later responding in the shuttle box. Inescapable shock in the harness and failure to escape in the shuttle box produced interference with escape responding after a 7-day rest. These results were interpreted as supporting a learned "helplessness" explanation of interference with escape responding: Ss failed to escape shock in the shuttle box following inescapable shock in the harness because they had learned that shock termination was independent of responding.

Reciprocal signalling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain mechanisms. Neuronal excitability can be powerfully enhanced both by classical neurotransmitters derived from neurons, and by immune mediators released from CNS-resident microglia and astrocytes, and from infiltrating cells such as T cells. In this Review, we discuss the current understanding of the contribution of central immune mechanisms to pathological pain, and how the heterogeneous immune functions of different cells in the CNS could be harnessed to develop new therapeutics for pain control. Given the prevalence of chronic pain and the incomplete efficacy of current drugs — which focus on suppressing aberrant neuronal activity — new strategies to manipulate neuroimmune pain transmission hold considerable promise.

The degree of behavioral control that an organism has over a stressor is a potent modulator of the stressor's impact; uncontrollable stressors produce numerous outcomes that do not occur if the stressor is controllable. Research on controllability has focused on brainstem nuclei such as the dorsal raphe nucleus (DRN). Here we find that the infralimbic and prelimbic regions of the ventral medial prefrontal cortex (mPFCv) in rats detect whether a stressor is under the organism's control. When a stressor is controllable, stress-induced activation of the DRN is inhibited by the mPFCv, and the behavioral sequelae of uncontrollable stress are blocked. This suggests a new function for the mPFCv and implies that the presence of control inhibits stress-induced neural activity in brainstem nuclei, in contrast to the prevalent view that such activity is induced by a lack of control.

The brain and immune system form a bidirectional communication network in which the immune system operates as a diffuse sense organ, informing the brain about events in the body. This allows the activation of immune cells to produce physiological, behavioral, affective, and cognitive changes that are collectively called sickness, which function to promote recuperation. Fight-flight evolved later and coopted this immune-brain circuitry both because many of the needs of fight-flight were met by this circuitry and this cooptation allowed the immune system to respond to potential injury in anticipatory fashion. Many sequelae of exposure to stressors can be understood from this view and can take on the role of adaptive responses rather than pathological manifestations. Finally, it is argued that activation of immune-brain pathways is important for understanding diverse phenomena related to stress such as depression and suppression of specific immunity.