Learned helplessness test

Another, somewhat comparable paradigm is the so-called learned helplessness test. Initially the rat is confronted with mild foot-shocks from which it cannot escape. Once it has learned that there is no way to avoid the unpleasant... 

Obviously one limitation of all this work is that the drug effects have been tested in normal animals. So far, the neurochemical changes induced by long-term drug treatment have not been tested in combination with procedures such as learned helplessness, but it cannot be assumed that they will be the same as those in normal (non-depressed) subjects. 

Unpredictability also is a central feature in the concept of learned helplessness. This concept, using uncontrollable shock, was introduced by Overmier and Seligman (1967) and is based on the observation that animals exposed to an invariable stressor such as electric foot shock, which, due to the experimental set-up, is uncontrollable in nature, developed behavioral deficits. As first shown by Weiss (1968), rats exposed to uncontrollable shock showed significant weight loss due to decreased food and water intake. Moreover, these animals spent more time immobile in the forced swim test, and they revealed altered sleep patterns as well as a weakened response to previously rewarding brain stimulation, i.e., anhedonia (Henn et al. 1985 Weiss 1991). Importantly, these changes are not seen in animals that receive the same shocks but can exert control over their duration. 

Upregulation of CREB could play an important role in the actions of antidepressant treatment. To directly test this hypothesis, the influence of CREB expression in models of depression has been examined. For these studies, the expression of CREB or a dominant-negative mutant of CREB (mCREB) is increased by viral mediated gene transfer or by inducible transgenic expression. In addition, the influence of null mutation of one isoform, a-CREB, on behavior has been studied. Viral expression of wild-type CREB in the hippocampus, where antidepressant treatment increases CREB, results in an antidepressantlike effect in the forced swim (FST) and learned helplessness (LH) paradigms (Chen et al. 2001). The results demonstrate that increased expression of CREB is sufficient to produce an antidepressant effect and support the hypothesis that this transcription factor is an important target of antidepressant treatment. 

Learned helplessness effective (EDS0) in 50% of the test population. Behavioural phenomenon consisting of passivity and withdrawal after exposure to an uncontrollable adverse event. 

The forced swim test [2,3], a model of learned helplessness or of behavioral despair, is conducted by forcing a rat or mouse to swim in an inescapable container filled with water. When placed in a swim tank, animals display escape-directed behaviors such as swimming, climbing, and diving. After an initial period of activity, animals become immobile or simply float in the water, using small movements to keep the head or nose above the water surface. The immobility (failure in the persistence of escape-directed behaviors) is frequently interpreted as despair-like behavior in which the subject has failed at escape attempts and adopts hopeless or depressed postures. 

Opioid peptides have also been tested in animal models of depression and of antidepressant activity. Enkephalins and endorphins decreased immobility in the forced swim test and in the learned helplessness paradigm, demonstrating... 

In the learned helpless model, animals (usually rats) are subjected to a brief (l-2h) inescapable shock. Subsequently, they are tested in a task in w hich they can terminate the shock by an operant response. Animals w ith prior inescapable shock exposure do not perform as w ell in the test (Maier and Watkins, 2005). Advantages of the learned helplessness model include its use in studies of neurochemical changes, and that it responds to repeated, rather than acute, antidepressant drug adminish ation. Disadvantages of the model include its dependence on acute stress adminish ation, suggesting it may better model posthau-madc stress disorder than major depressive disorder. 

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