The ability to shift between different behavioral strategies is necessary for appropriate decision-making. Here, we show that chronic stress biases decision-making strategies, affecting the ability of stressed animals to perform actions on the basis of their consequences. Using two different operant tasks, we revealed that, in making choices, rats subjected to chronic stress became insensitive to changes in outcome value and resistant to changes in action-outcome contingency. Furthermore, chronic stress caused opposing structural changes in the associative and sensorimotor corticostriatal circuits underlying these different behavioral strategies, with atrophy of medial prefrontal cortex and the associative striatum and hypertrophy of the sensorimotor striatum. These data suggest that the relative advantage of circuits coursing through sensorimotor striatum observed after chronic stress leads to a bias in behavioral strategies toward habit.

Depression, a complex mood disorder, displays high comorbidity with anxiety and cognitive disorders. To establish the extent of inter-dependence between these behavioral domains, we here undertook a systematic analysis to establish interactions between mood [assessed with the forced-swimming (FST) and sucrose consumption tests (SCT)], anxiety [elevated-plus maze (EPM) and novelty suppressed feeding (NSF) tests] and cognition (spatial memory and behavioral flexibility tests) in rats exposed to unpredictable chronic-mild-stress (uCMS). Expectedly, uCMS induced depressive-like behavior, a hyperanxious phenotype and cognitive impairment; with the exception of the measure of anxiety in the EPM, these effects were attenuated by antidepressants (imipramine, fluoxetine). Measures of mood by the FST and SCT were strongly correlated, whereas no significant correlations were found between the different measures of anxiety (EPM and NSF); likewise, measures of cognition by spatial memory and behavioral flexibility tests were poorly correlated. Inter-domain analysis revealed significant correlations between mood (FST and SCT) and anxiety-like behavior (NSF, but not EPM). Furthermore, significant correlations were found between cognitive performance (reverse learning task) and mood (FST and SCT) and anxiety-like behavior (NSF). These results demonstrate interactions between different behavioral domains that crosscut the disciplines of psychiatry and neurology.

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Chronic pain syndromes encompass several clinical entities that frequently affect the individuals' emotional and cognitive behaviours which, in turn, can also alter pain perception. Additionally, both pain perception and motivational-affective behaviours change with increasing age. In order to evaluate the influence of age upon the interaction between chronic pain and affective/cognitive behaviours, 3-, 10- and 22-month-old rats with 1 month neuropathy (spared nerve injury, SNI model) were compared with age-matched sham-operated controls in the open field (OF; locomotor and exploratory behaviours), elevated plus-maze (EPM; anxiety-like behaviour), forced swimming (FST; depressive-like behaviour), working memory water maze (WM; spatial short-term memory), Morris water maze (MWM; spatial reference memory) and spatial reversal (behavioural flexibility) tests. Locomotor and exploratory activities decreased steadily with age and were further reduced by SNI. Aging was associated with increased anxiety-like behaviour, which was potentiated by SNI in both 3- and 22-month-old rats. The performance in the FST was affected by SNI but only in mid-aged animals. Cognitive performances in the MWM and spatial reversal tests deteriorated with age; however, the SNI lesion was only detrimental in the reversal task to mid-aged animals. Our data demonstrate that the influence of neuropathic pain on affective and cognitive behaviours is age dependent and varies with the behavioural domain that is tested. Importantly, mid-aged animals seem to be more susceptible to depression and cognitive deterioration associated to chronic pain than young and old groups.

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