Learned helplessness model

Tejedor-Real P, Mico JA, Maldonado R, Roques BP, Gibert-Rahola J. (1995). Implication of endogenous opioid system in the learned helplessness model of depression. Pharmacol Biochem Behav. 52(1) 145-52. 

Sayamwong Hammack Jom earned his Ph.D. from the University of Colorado studying how the serotonin system is altered in the learned helplessness model, which produces an anxiety-like state. He continues to research serotonin influences on anxiety in his current position as a postdoctoral fellow at Emory University. His work has been published in such journals as The Journal of Neuroscience, Neuroscience, and Behavioral Neuroscience. He currently lives in Atlanta, Georgia, with his wife. Heather. He would like to dedicate his contribution to this book to his parents. 

The picture with CREB is far from straightforward. Increased expression of CREB in the nucleus accumbens of rats produces depression-like effects, which include anhedonia (77, 89) and increased helplessness, in learned-helplessness models (81). Increases in BDNE expression in the mesolimbic DA system of rats are associated with induction of depressive effects in certain animal models. However, studies that use systemic administration of BDNE and activators of the cAMP-CREB cascade seem to have a net therapeutic effect in behavioral models of depression (90, 86, 89, 95). 

Of stressful life events, those which are unpleasant or represent loss, and over which the person has no control, are more likely to lead to major depression, according to the learned helplessness model. In this model, inescapable and unpleasant stress leads to the belief that one s response cannot influence outcomes, hence learned helplessness (Seligman 1972). This is considered a depressive cognitive attribution, and changing these negative thought patterns is the basis for cognitive psychotherapy. 

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. 

The learned helplessness model, in which depression is seen to emerge when people (or animals) perceive that "No matter what I do, I have no ability to influence aversive experiences" (Seligman)... 

Porsolt RD, Martin P, Lenegre A, Fromage S, Drieu K. (1990). Effects of an extract of Ginkgo biloba (EGB 761) on "learned helplessness" and other models of stress in rodents. Pharmacol Blochem Behav. 36(4) 963-71. 

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. 

Ron an PJ, Kramer GL, Petty F (2001) Corticotropin releasing factor and arginine vasopressin effects in the learned helplessness animal model. Soc Neurosci Meeting Abstr 414.20 Rosen JB, Schulkin J (1998) From normal fear to pathological anxiety. Psychol Rev 105 325-350... 

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... 

Several animal models of depressive disorders have been studied, and space does not permit detailed review of these findings. Animal models of depression have fallen into three general categories Stress induced, ethologically relevant, and genetic (Machado-Vieira et al., 2004). Of the stress-induced models, learned helplessness, chronic mild sh ess, and forced sw im (behavioral despair) are best characterized (Willner and Mitchell, 2002). 

Interestingly, in the learned helplessness animal model of depression, reversal of helpless behavior may be obtained acutely by direct intracerebral drug administration into frontal cortex, though reversal of helpless behavior by systemic drug administration requires several days (Sherman and Petty, 1980). This suggests that the reversal of depressive symptoms by antidepressant drugs may involve pharmacokinetic as well as pharmacodynamic effects (Petty et al., 1982). 

Weiss, J., H. I. Glazer, and L. A. Pohorecky. 1976. Coping behavior and neurochemical changes in rats An alternative explanation for the original "learned helplessness" experiments. In Animal models in human psychobiology, G. Servan and A. Kling, eds. New York Plenum Press. 

Another behavioural syndrome, called learned helplessness can be induced in dogs by presenting an inescapable traumatic event, e.g. electric shock in a shuttle box. When later confronted with a signalled escape-avoidance situation, two thirds of the animals develop a typical passive state and become helpless . The development of helplessness in rats has been correlated with a depletion of brain NA, and when atropine is injected directly into the septal brain area of cats, their previously induced helplessness is cured [29]. Recently, a new animal model useful for screening potential antidepressive compounds has been described [30]. When rats are forced to swim in an inescapable situation, they will stop swimming and develop an immobility. The duration of this state of immobility can be shortened by treatment with antidepressants. 

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