Elsevier

Neuropharmacology

Volume 62, Issue 2, February 2012, Pages 565-575
Neuropharmacology

Invited review
Overlapping neurobiology of learned helplessness and conditioned defeat: Implications for PTSD and mood disorders

https://doi.org/10.1016/j.neuropharm.2011.02.024Get rights and content

Abstract

Exposure to traumatic events can increase the risk for major depressive disorder (MDD) as well as posttraumatic stress disorder (PTSD), and pharmacological treatments for these disorders often involve the modulation of serotonergic (5-HT) systems. Several behavioral paradigms in rodents produce changes in behavior that resemble symptoms of MDD and these behavioral changes are sensitive to antidepressant treatments. Here we review two animal models in which MDD-like behavioral changes are elicited by exposure to an acute traumatic event during adulthood, learned helplessness (LH) and conditioned defeat. In LH, exposure of rats to inescapable, but not escapable, tailshock produces a constellation of behavioral changes that include deficits in fight/flight responding and enhanced anxiety-like behavior. In conditioned defeat, exposure of Syrian hamsters to a social defeat by a more aggressive animal leads to a loss of territorial aggression and an increase in submissive and defensive behaviors in subsequent encounters with non-aggressive conspecifics. Investigations into the neural substrates that control LH and conditioned defeat revealed that increased 5-HT activity in the dorsal raphe nucleus (DRN) is critical for both models. Other key brain regions that regulate the acquisition and/or expression of behavior in these two paradigms include the basolateral amygdala (BLA), central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST). In this review, we compare and contrast the role of each of these neural structures in mediating LH and conditioned defeat, and discuss the relevance of these data in developing a better understanding of the mechanisms underlying trauma-related depression.

This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’.

Highlights

► We review two animal models associated with exposure to an acute traumatic event during adulthood. ► We compare and contrast the neural changes that mediate both models. ► We discuss how these animal models provide a better understanding of PTSD and mood disorders.

Section snippets

Animal models

Multiple animal paradigms have been argued to model both PTSD and MDD, which may reflect that these disorders share similar symptoms and/or have a similar biological basis. Animal models of depression have often been evaluated on the basis of several criteria: whether they produce behavioral changes that are similar to those observed in depression, whether these changes can be objectively measured, and whether these changes can be reversed by treatments used to treat depression (McKinney and

Learned helplessness

In humans, trauma requires the experience or witnessing an actual or threatened death, serious injury or threat to the physical integrity of self or others, and the response to this event must involve intense fear, helplessness or horror (APA, 2000). While it is not possible to determine how animals interpret laboratory stressors, behavioral correlates of fear can be assessed, and the controllability of laboratory stressors can be manipulated to produce situations in which animals are made

Conditioned defeat

Social defeat is a robust stressor that, like LH, produces an array of behavioral changes including anxiety- and depression-like behavior (Berton et al., 1998, Heinrichs et al., 1992, Keeney et al., 2006, Krishnan et al., 2007, Rodgers and Cole, 1993). In Syrian hamsters, social defeat leads to a loss of species-typical territorial aggression and increased submissive and defensive behavior in subsequent social encounters with smaller non-aggressive intruders. This phenomenon has been called

New directions

As discussed above, it is likely that the brain regions implicated in LH and conditioned defeat are important targets for current pharmacological approaches in the treatment of MDD and PTSD, and we have previously suggested that changes in the 5-HT response of brain regions like the BNST and DRN mediate the efficacy of some of these treatments (Hammack et al., 2009b, also see Berendsen, 1995, Stahl, 1994, Strome et al., 2005, Yatham et al., 1999). However, the data described above suggest that

Conclusions

The LH and conditioned defeat paradigms produce behavioral changes that may be associated with the symptomatology of trauma-related depression. A consideration of the neural circuitry underlying each of these behavioral paradigms suggests that the DRN, BNST, BLA, and CeA play a critical role in the acquisition and expression of these behavioral changes, although the precise role of these structures may differ depending on the behavioral paradigm studied. Based on these studies, it seems clear

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