| Learned helplessness is an animal model of co-morbid anxiety and depression whereby exposure to a prolonged series of uncontrollable, inescapable shocks produces behavioral deficits twenty-four hours later. The history of learned helplessness is presented and reviewed. The present state of learned helplessness theory is reviewed with particular attention to the metabolic based anxiety hypothesis, (Minor, Chang & Winslow).; The anxiety hypothesis argues that exposure to inescapable shock produces chronic fear. Some unknown result of this chronic fear creates the conditions for energy failure twenty-four hours later. When rechallenged the subjects undergo a quick transition from a state of over-sensitization to a state of energy failure. This energy failure produces compensatory adenosine regulation. Adenosine regulation protects the neurons from the potentially fatal effects of energy failure but also renders them unable to deal with the task demands and thus is the proximate cause of the behavioral deficits.; Three experimental sets were run to examine the role of metabolic failure in the learned helplessness paradigm. The first experiment tested whether increasing endogenous adenosine levels are necessary and sufficient to produce behavioral impairments on a shuttle-escape task. The second experiment examined if metabolic failure would produce adenosine regulated behavioral deficits similar to those seen following inescapable shock. The third experiment measured the metabolic and neural activity levels during the pretreatment session to identify neural regions differentially activated by escapable and inescapable shock.; The results from the three experimental sets strongly supported the adenosine hypothesis and a presence of a compromised energy metabolism in the learned helplessness effect. Experiment set 1 found that increased endogenous adenosine levels in the central nervous system are necessary and sufficient to produce learned helplessness. Experiment set 2 found that metabolic failure produced adenosine mediated behavioral deficits behavioral indistinguishable from the deficits produced by inescapable shock. Experiment set 3 found evidence for different metabolic and neural activities in the retrosplenial cortex, anterior thalamus, dorsal raphe, locus coeruleus, hippocampus and hypothalamus. The potential functional pathway in these regions is discussed. |
