The forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are... Show moreThe forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are anthropomorphic interpretations of the rodent's acquired immobility. Rather, the transition from swimming to immobility allows to examine the mechanistic underpinning of coping with inescapable stressors. However, in a recent detailed analysis of the FST application over the past 40 years, we noted a dramatic surge in the use of this test to phenotype animals as 'depressed'. As a follow up to that report, we now present an analysis of the use of the FST over the past three years. This literature analysis shows that the popularity of the EST is still increasing and that the majority of researchers qualifies the rodent's floating response as depressive-like behavior. However, over the past few years we also note a trend to interpret immobility rather as the expression of a coping strategy. In view of this result, we have sent a poll to the relevant authors to learn how consistent they are in naming FST behavior. Remarkably, we find a dramatic inverse correlation between their first qualification of acquired immobility as depressive-like behavior towards their current interpretation as coping strategy. In this contribution we have embedded our literature analysis and poll results in an update on the management of coping with inescapable stressors by processing in prefrontal cortical circuitry and glucocorticoid feedback. Show less
The forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are... Show moreThe forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are anthropomorphic interpretations of the rodent’s acquired immobility. Rather, the transition from swimming to immobility allows to examine the mechanistic underpinning of coping with inescapable stressors. However, in a recent detailed analysis of the FST application over the past 40 years, we noted a dramatic surge in the use of this test to phenotype animals as ‘depressed’. As a follow up to that report, we now present an analysis of the use of the FST over the past three years. This literature analysis shows that the popularity of the FST is still increasing and that the majority of researchers qualifies the rodent’s floating response as depressive-like behavior. However, over the past few years we also note a trend to interpret immobility rather as the expression of a coping strategy. In view of this result, we have sent a poll to the relevant authors to learn how consistent they are in naming FST behavior. Remarkably, we find a dramatic inverse correlation between their first qualification of acquired immobility as depressive-like behavior towards their current interpretation as coping strategy. In this contribution we have embedded our literature analysis and poll results in an update on the management of coping with inescapable stressors by processing in prefrontal cortical circuitry and glucocorticoid feedback. Show less
Obesity and sleep disturbances comprise major health problems which are likely interrelated. Diet-induced obesity in young mice has been demonstrated to lead towards an altered sleep homeostasis.... Show moreObesity and sleep disturbances comprise major health problems which are likely interrelated. Diet-induced obesity in young mice has been demonstrated to lead towards an altered sleep homeostasis. In the current study, we investigated the effect of chronic (12 weeks) high-caloric diet (HCD, 45% fat) consumption on sleep and the sleep electroencephalogram (EEG) in young and older mice (6-month-old, n = 9; 18-month-old, n = 8 and 24-month-old, n = 4) and compared with age-matched controls on normal chow (n = 11, n = 9 and n = 9 respectively). Half of the 24-month-old mice did not cope well with HCD, therefore this group has a lower n and limited statistical power. We recorded EEG and the electromyogram for continuous 48-h and performed a 6-h sleep deprivation during the second day. In aged HCD fed mice (18 months old) compared to young, an aging effect was still evident, characterized by decreased waking and increased NREM sleep in the dark period, decreased REM sleep during the light period, as well as increased slow-wave-activity (SWA, EEG power in NREM sleep in 0.5–4.0 Hz). Additionally, aged HCD treated mice showed increased NREM sleep and decreased waking, compared to age-matched controls, denoting an enhanced aging phenotype in the sleep architecture. Notably, an overall increase was found in the slow component of SWA (0.5–2.5 Hz) in aged HCD fed mice compared to age-matched controls. Our data suggest that the effect of aging is the dominant variable irrespective of diet. However, a synergistic effect of aging and diet is noted indicating that chronic HCD consumption exacerbates age-associated sleep alterations. Show less
Abstract Background: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a... Show moreAbstract Background: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a general psychopathology factor (GPF) associated with risk for multiple psychiatric disorders. It is, however, unknown how GPF relates to white matter integrity (WMI). In the current diffusion tensor imaging (DTI) study, we examined how GPF relates to abnormalities in a skeleton representation of white matter tracts, taking into account a trans-diagnostic risk factor: unresolved-disorganized attachment (Ud) resulting from loss or trauma. Methods: Unique associations between GPF, Ud, and WMI were examined in a combined sample of adolescents (N = 63) with childhood sexual abuse-related posttraumatic stress disorder (N = 18), anxiety and depressive disorders (N = 26) and without psychiatric disorder (N = 19). WMI was measured using DTI. Ud was measured using the Adult Attachment Interview. We controlled for puberty stage, gender, age, and IQ. Results: Controlling for GPF, Ud was associated with reduced fractional anisotropy (FA) in the splenium and inferior fronto-occipital fasciculus (IFOF). Controlling for Ud, GPF was associated with reduced FA in the genu and body of the corpus callosum. Conclusions: Decreasing WMI in the genu and body with increasing psychopathology across diagnoses suggests demyelinization in these areas and may underlie comorbidity and presence of symptoms that transcend psychopathological diagnoses. In contrast, trauma-related WMI reductions in the splenium and IFOF may account for heterogeneity within diagnostic categories as a function of childhood trauma. These findings support the importance of a dimensional approach in addition to traditional diagnostic classifications in clinical research and practice. Keywords: Adversity, Child abuse, Psychopathology, Attachment, Brain imaging Show less
Stress induces a switch in learning strategies of male C57BL/6J mice from predominantly spatial to more stimulus-response learning. To study generalization of these findings over sex, we... Show moreStress induces a switch in learning strategies of male C57BL/6J mice from predominantly spatial to more stimulus-response learning. To study generalization of these findings over sex, we investigated female C57BL/6J mice at three phases of the estrous cycle under non stress and acute (10 mm) restraint stress conditions. On a circular hole board (CHB) task, about half of the naive female mice used spatial and stimulus-response strategies to solve the task. Under stress, female mice favored spatial over stimulus-response strategies, with 100% of female mice in the estrus phase. Performance expressed as latency to solve the task is only improved in stressed female mice in the estrus phase. We conclude that the use of learning strategies is influenced by sex and this difference between sexes is aggravated by acute stress. (C) 2012 Elsevier B.V. All rights reserved. Show less
Fauth-Buhler, M.; Rover, M. de; Rubia, K.; Garavan, H.; Abbott, S.; Clark, L.; ... ; Robbins, T.W. 2012
The current study provides a detailed description of the pattern of exploratory behaviors encountered in adult zebrafish when exposed to a novel/unfamiliar environment using the light/dark box and... Show moreThe current study provides a detailed description of the pattern of exploratory behaviors encountered in adult zebrafish when exposed to a novel/unfamiliar environment using the light/dark box and open field tests. We also document the impact of an acute stressor (restraint stress) given just prior the onset of behavioral testing. We report the following main findings: (1) zebrafish display anxiety-like behaviors including dark-avoidance (in light/dark box test) and thigmotaxis (in open field test), (2) upon exposure to a novel environment (first 2 min), zebrafish display place preference for the outer zone of the testing apparatus where they seek escape via the transparent wall, and exhibit high locomotor activity accompanied by high swimming speed, (3) thigmotaxis, behavioral hyperactivity, and swimming speed habituate (decrease) over time, (4) prior history of stress attenuates the natural tendency to engage in dark-avoidance behavior and thigmotaxis, reduces attempts to escape via the transparent wall, and greatly increased behavioral hyperactivity and swimming speed. Stress-induced patterns of behavior normalize to levels comparable to that of non-stressed controls by the end of the 5-min test session. Taken together, these findings suggest that novel environment can elicit anxiety-like behaviors in zebrafish such as dark-avoidance and thigmotaxis and the prior history of stress greatly affects patterns of exploration, defensive behaviors, and coping strategies in the light/dark box and open field tests. These findings are consistent with previous findings in rodents and support the usefulness of such behavioral paradigms in zebrafish. (C) 2010 Elsevier B.V. All rights reserved. Show less
Schwabe, L.; Schachinger, H.; Kloet, E.R. de; Oitzl, M.S. 2010
Recent evidence indicates that stress modulates multiple memory systems, favoring caudate nucleus-based stimulus-response learning at the expense of hippocampus-based spatial learning. Whether this... Show moreRecent evidence indicates that stress modulates multiple memory systems, favoring caudate nucleus-based stimulus-response learning at the expense of hippocampus-based spatial learning. Whether this is due to a facilitating effect of stress on stimulus-response learning, an impairing effect on spatial learning, or both, is not known. To answer this question, mice were either subjected to restraint stress, injected with vehicle or corticosterone or left untreated before training in two circular hole board tasks that could discriminate spatial and stimulus-response strategies. Stress, vehicle and corticosterone injection all impaired learning performance in the spatial task. Conversely, performance in the stimulus-response task was not affected by stress or corticosterone injection, although performance was generally lower than in the spatial task. Irrespective of the treatment, mice had to overcome the preference to use their spatial memory system to achieve the stimulus-response task. These findings suggest that (i) the caudate nucleus-based memory system is less stress sensitive than the hippocampus-based system and may thus dominate behavior in situations of stress and (ii) that multiple memory systems may compete for control of behavior even in tasks that can solely be solved by one system. (C) 2010 Elsevier B.V. All rights reserved. Show less
