Abstract
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.
Highlights
Psychiatric disorders, including depression, are complex and heterogeneous clinical entities
The tricyclic agent imipramine exhibited an earlier onset of antidepressant action; this drug reversed anhedonic behavior within the first week of treatment (P < 0.001), whereas the responses to the selective serotonin reuptake inhibitors (SSRI) fluoxetine only appeared after 2 weeks (P < 0.001)
Antidepressant treatment proved to be a significant factor in recovery from learned helplessness as evaluated in the forced swimming test (FST) (F2,52 = 27.962, P < 0.001); when compared to stressed rats that did not receive drug treatments, immobility time was significantly reduced by fluoxetine (P < 0.001) and imipramine (P < 0.001) and the latency time to immobility was significantly increased by both drugs (P < 0.001)
Summary
Psychiatric disorders, including depression, are complex and heterogeneous clinical entities. In the absence of well defined pathophysiological factors at the cellular and molecular level, the clinical definition and classification of depression has been structured in diagnostic tools such as the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the International Classification of Diseases and Related Health Problems (ICD-10). This syndromatic approach relies in the clustering of core psychopathological phenomena that characterize a depressive state. The subjective separation of these three behavioral dimensions – depressive mood, anxiety and impaired cognition – while practical for diagnostic classification purposes and for their modelling, tends to hinder understanding of the individual and synergistic contributions of these dimensions to the overall features of the clinical disorder
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