ReviewNeurochemical modulation of stress-induced cognitive inflexibility in a rat model of an attentional set-shifting task
Introduction
Chronic stress may precipitate or exacerbate many psychiatric disorders, including depression, due to its detrimental effects on many brain functions. The impact of stress on the brain is complex, though some regions, such as the hippocampus, amygdala and prefrontal cortex, seem to be key targets for stressinduced structural, physiological and functional alterations [25]. Experimental evidence suggests that the prefrontal cortex may be particularly susceptible to stress exposure [21]. Of particular note is the fact that many frontal-governed cognitive processes show declines as a result of stress-related disorders. Animal models of the effects of stress on frontal functions have been developed to elucidate the mechanisms underlying these disorders as well as for the development of novel strategies for their treatment.
Section snippets
Stress-induced dendritic remodeling in the rat prefrontal cortex
Chronic stress produces profound changes in the morphology of neurons in the rodent medial prefrontal cortex (mPFC). Indeed, the initial findings of Cook and Wellman [13], demonstrating that 3 weeks of restraint evoked apical dendritic retraction and debranching in mPFC neurons in rats, have been confirmed in a number of subsequent studies [9, 28, 44]. Moreover, it has been demonstrated that the morphology of the mPFC is exquisitely sensitive to stress, as dendritic remodeling occurred in
Stress and prefrontal functions
It is likely that dendritic remodeling in the prefrontal cortex may underlie functional deficits. Specifically, an impairment in set-shifting ability, which is a sensitive indicator of cortical processing, has been connected to stress-evoked disruption [28]. The next paragraphs briefly describe the attentional set-shifting task and the impact of stress procedures on rats’ performance on the task.
Neurochemical basis of stress-induced prefrontal deficits
The mechanisms that mediate morphological and functional changes in the mPFC are interrelated and complex. Exposure to stressors results in a variety of neurochemical changes in prefrontal cortex, including glucocorticoids and the monoaminergic and glutaminianergic systems. The following paragraph will briefly summarize experimental data on the potential involvement of these neurochemical substrates in stress-induced cognitive inflexibility.
Antidepressant drugs and stress-induced cognitive inflexibility
Because prolonged stress is a major risk factor for depression, stress-based animal models represent a useful instrument for mimicking depressive-like symptomatology [1] and have been used to find novel antidepressants [55]. Most of these studies have been focused on the anti-anhedonic action of compounds with potential antidepressant-like activity. It should, however, be noted that, in addition to mood disturbances, cognitive deficits represent an integral feature of depressive disorder.
Concluding remarks
The available research tools have only begun to reveal all of the possible stress-brain interactions and their consequences. Recent studies have also found gender differences in the response of cortical morphology to stress [47]. It remains to be determined whether this diversity in structural changes may also be translated to altered functions. Another unresolved question is the potential functional implication of the recently demonstrated circuit specificity of stress-evoked morphological
Acknowledgments
This work was supported by the grant POIG.01.01.02-12-004/09. Depression – mechanisms – therapy., which was co-financed by the European Union from the European Fund of Regional Development (EFRD)
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