Robert Murison - Academia.edu (original) (raw)
Papers by Robert Murison
Translational Psychiatry, 2016
Sexual abuse contributes to the development of multiple forms of psychopathology, including anxie... more Sexual abuse contributes to the development of multiple forms of psychopathology, including anxiety and depression, but the extent to which genetics contributes to these disorders among sexual abuse victims remains unclear. In this translational study, we first examined gene expression in the brains of rodents exposed to different early-life conditions (long, brief or no maternal separation). Hypothesizing that genes revealing changes in expression may have relevance for psychiatric symptoms later in life, we examined possible association of those genes with symptoms of anxiety and depression in a human sample of sexual abuse victims. Changes in rodent brain gene expression were evaluated by means of correspondence and significance analyses of microarrays by comparing brains of rodents exposed to different early-life conditions. Tag single-nucleotide polymorphisms (SNPs) of resulting candidate genes were genotyped and tested for their association with symptoms of anxiety and depress...
Scientific reports, Jan 27, 2017
Enzyme-linked immunosorbent assay (ELISA) kits are widely used to quantify corticosterone levels ... more Enzyme-linked immunosorbent assay (ELISA) kits are widely used to quantify corticosterone levels for the assessment of stress in laboratory animals. The aim of this experiment was simply to evaluate if four different and widely used commercial ELISA assays would yield the same or similar values of corticosterone in serum samples taken from laboratory rats after the mild stress of being held for sampling blood from the saphenous vein. Trunk blood was sampled from 32 male Wistar rats 30 minutes after this mild stress exposure and analysed with each of four commercial ELISA kits. Both the Arbor Assays and the DRG-4164 kits were significantly higher than the DRG-5186 and the Enzo kits. There were no significant differences between the DRG-5186 and Enzo kits. Overall the correlations between kits were high. In conclusion, the commercial ELISA kits tested in the present experiment yielded different values of total corticosterone in the same serum samples. The precision in determining true...
Journal of biological rhythms, 2016
Millions of people worldwide are working at times that overlap with the normal time for sleep. Sl... more Millions of people worldwide are working at times that overlap with the normal time for sleep. Sleep problems related to the work schedule may mediate the well-established relationship between shift work and increased risk for disease, occupational errors and accidents. Yet, our understanding of causality and the underlying mechanisms that explain this relationship is limited. We aimed to assess the consequences of night-shift work for sleep and to examine whether night-shift work-induced sleep disturbances may yield electrophysiological markers of impaired maintenance of the waking brain state. An experimental model developed in rats simulated a 4-day protocol of night-work in humans. Two groups of rats underwent 8-h sessions of enforced ambulation, either at the circadian time when the animal was physiologically primed for wakefulness (active-workers, mimicking day-shift) or for sleep (rest-workers, mimicking night-shift). The 4-day rest-work schedule induced a pronounced redistri...
Animal Models, Volume II, 2002
The open dentistry journal, 2015
Early life adverse events may influence susceptibility/resistance to chronic inflammatory disease... more Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. Compared to undisturbed controls, MD rats developed significantly more periodon...
Psychoneuroendocrinology, 2005
Proceedings of the National Academy of Sciences, 2002
The hippocampus has a critical role in several fundamental memory operations, including the condi... more The hippocampus has a critical role in several fundamental memory operations, including the conditioning of fear to contextual information. We show that the hippocampus is necessary also for unconditioned fear, and that the involved circuitry is at the ventral pole of the hippocampus. Rats with selective hippocampal lesions failed to avoid open arms in an elevated plus-maze and had decreased neuroendocrine stress responses during confinement to a brightly lit chamber. These effects were reproduced by lesions of the ventral half of the hippocampus, but not by damage to the dorsal three-quarters of the hippocampus or the amygdala. Ventral lesions failed to impair contextual fear conditioning or spatial navigation, suggesting that the ventral hippocampus may specifically influence some types of defensive fear-related behavior.
PLoS ONE, 2013
Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neur... more Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.
Physiology & Behavior, 2008
Social stressors play a major role in the pathogenesis of affective disorders like anxiety and de... more Social stressors play a major role in the pathogenesis of affective disorders like anxiety and depression. These disorders are associated with altered behaviour (i.e. locomotor activity, harm avoidance, startle response, anhedonia and sexual behaviour), sleep alterations and abnormalities in the stress response. The animal social defeat (SD) model is based on a natural conflict situation where a male intruder rat eventually subordinates itself to an unfamiliar territorial resident conspecific. The effects of defeat are studied in the intruder rat. The main purpose was to study the face validity of the SD model for affective disorders by investigating short-term and long-term consequences of single and/or double exposure to SD on behaviour and sleep in rats. In particular, the intention was to evaluate if SD could reproduce the alterations in locomotor activity, harm avoidance, startle response, anhedonia, sexual behaviour, stress responses and sleep parallel to those observed in patients with affective disorders. Social defeat induced low activity in the central sector of the open field (OF) (Paper I), indicating high harm avoidance which may reflect anxiety-like or depression-like behaviour. No short-term or long-term effects were seen on total locomotor activity in the OF (Papers I and II). Further, a lack of habituation to the OF across days was seen, which may reflect long-lasting heightened anxiety (Papers I and III). Overall, in the elevated plus maze (EPM) test, SD rats showed less total locomotor activity, less percentage time and less activity on the open arms, lasting up to 3 weeks after defeat (Paper II), possibly reflecting anxiety-like behaviours. High acoustic startle responses (ASR) were seen as a long-term effect of SD, probably reflecting an anxiety-like state (Paper II). A short-lasting reduced preference for sucrose was seen (Paper II), indicating an anhedonic state that may be interpreted as a transient anxiety-like symptom. Sexual behaviour was not affected (Paper I). As a group, SD rats did not show altered corticosterone responsiveness to OF exposure (Paper III). The SD rats showed a short-term increase in duration of slow wave sleep (SWS) 2 and sleep fragmentation (Paper I). Overall, SD rats did not show long-term effects on sleep or EEG power (Paper III). The effects of SD on sleep may be vii interpreted as anxiety, because they were short-lasting and the common sleep alterations seen in depression were not induced (e.g. reduced SWS2 and REM sleep alterations). A secondary aim was to compare effects of SD to the effects of inescapable footshock (IFS) (Paper II). The two stressors induced a similar short-term effect on sucrose preference and similar long-term anxiety-like behaviours in the EPM test. Contrary to what was expected, SD rats showed the highest ASR, while IFS rats showed the lowest total activity in the OF test. The results may reflect fundamental differences between SD and IFS. Another secondary aim was to explore the relationship between levels of corticosterone prior to SD or IFS stressor, and the different post-stressor behaviours (Paper II). Low pre-stress corticosterone level was expected to be associated with anxiety-like behaviours following stress. Overall, such a relationship was not found. Contrary to what was expected, the SD rats with high pre-stressor corticosterone level showed the greatest ASR, while IFS rats with low pre-stress corticosterone level did not show alterations in ASR. This further supports differences between the SD and the IFS stressor. The final secondary aim was to investigate differences in effects of SD on behaviour and sleep in two subgroups of rats with different coping styles in the SD (Paper III). Contrary to what was expected, rats fighting back in the SD confrontation showed longer latency to leave the start box, and spent less time in the OF arena compared to those not fighting back, indicating anxiety-like behaviour. They also showed more fragmentation of sleep in SWS1 and SWS2. The results may suggest that rapid submission during SD may be more adaptive than surrender after a longer fight, given these outcome measures. In conclusion, the studies presented in this thesis show that exposure to SD induced both short-term and long-term consequences for multiple behavioural features and at least short-term consequences for sleep. The behavioural consequences of SD are different from those of IFS. The studies generally support a high degree of face value for the SD model as a model for affective disorders, more relevant to anxiety than to depression. viii List of publications This thesis is based on the following papers.
Physiology & Behavior, 2004
In this study, we investigated the effects of three neonatal conditions on adult corticosterone (... more In this study, we investigated the effects of three neonatal conditions on adult corticosterone (CORT) levels, acoustic startle responses (ASRs), and vulnerability to colitis induced by dextran sulfate sodium (DSS) and how these early manipulations might interact with a brief stress exposure in adulthood on the same measures. Infant animals were subjected daily to either 180-min maternal separation [prolonged maternal separation (LMS)], 10-min maternal separation [brief maternal separation (BMS)], or nonhandling (NH) conditions during postnatal days 1-14. As adults, half of the animals were exposed to a series of 10 uncontrollable foot shocks. Animals were tested for CORT levels prior to and 10 days following shock/nonshock procedures before being tested for ASRs. Finally, all animals were exposed to 4% DSS in their drinking water for 6 days. LMS animals showed enhanced vulnerability to DSS-induced colitis when previously exposed to shock and enhanced stress reactivity responses as shown by elevated startle and CORT levels. Among the nonshocked animals, NH animals showed most colonic damage. Taken together, the results support previous findings suggesting that BMS has a protective effect on adult stress exposure. Additionally, BMS protects the animals from chemically induced colitis. The NH condition has clearly an effect on sensitizing mucosal response to DSS exposure.
Pharmacology Biochemistry and Behavior, 2006
Chronic stress is linked to development of depression and may trigger neurobiological changes und... more Chronic stress is linked to development of depression and may trigger neurobiological changes underlying the disease. Downregulation of the secretory peptide brain-derived neurotrophic factor (BDNF) and the transcriptional regulator calcium/cyclic-AMP responsive binding protein (CREB) have been implicated in stress and depression-related pathology in animal studies. When animals are exposed to the chronic mild stress (CMS) protocol, multiple depression-like symptoms are observed. Here we investigated the effect of CMS on BDNF protein expression and CREB activation in the dentate gyrus and hippocampus proper. Rats exposed for 5 weeks to repeated, unpredictable, mild stressors showed reduced BDNF expression and inhibited phosphorylation of CREB (Ser-133) in the dentate gyrus (-25.0%+/-3.5% and -29.7+/-7.3%, respectively), whereas no significant effects were observed in the hippocampus proper. CMS-treated rats consumed less sucrose compared to control rats, indicating a state of anhedonia. Moreover, phospho-CREB levels in the dentate gyrus were positively correlated with the animals' sucrose intake at the end of the CMS protocol. These results couple chronic mild stress to a downregulation of CREB activity and BDNF protein expression specifically within the dentate gyrus and support the possibility that the BDNF-CREB system plays an important role in the response to environmental challenges.
The European Journal of Orthodontics, 2009
The aim of the study was to investigate the effect of emotional stress on apical root resorption ... more The aim of the study was to investigate the effect of emotional stress on apical root resorption (ARR) and tooth displacement during orthodontic tooth movement in rats. A further area of interest was to evaluate if the expression of interleukin-1 alpha (IL-1a) as well as the density and distribution of peptidergic nerve fibres immunoreactive to calcitonin gene-related peptide (CGRP) in the periodontal ligament (PDL) are associated with possible stress-induced changes in root resorption and tooth movement. A total of 52 male Wistar rats, aged 6 weeks, were divided in three experimental and one control group (n = 4). Group 1 had orthodontic tooth movement and received foot shocks (OTMS; n = 16), group 2 had orthodontic tooth movement but received no foot shocks (OTMNS; n = 16), and group 3 had no orthodontic tooth movement and received foot shocks (NOTMS; n = 16). Each group was further divided into four subgroups (n = 4), corresponding to the period of the experiment, i.e. 3, 7, 13, and 21 days. At the end of each experimental period, the blood samples were taken, the animals were sacrificed, and the jaws excised, deminerialized, and processed for immunocytochemistry. One-way analysis of variance was used to detect inter-group differences for all investigated variables. CGRP immunopositive nerve fibres were evaluated qualitatively. All the experimental groups demonstrated higher corticosterone levels than the control group, suggesting a stress-induced experience by orthodontic treatment per se. The OTMS group had the least amount of cellular cementum throughout the experimental periods and showed significant reduction in tooth displacement, especially at 3 and 7 days. No obvious changes were observed in the dental tissue expression of IL-1a and CGRP immunoreactive nerve fibres between the stressed and non-stressed orthodontically treated groups.
Brain Research, 1975
The effects of bilateral removal of the superior colliculus or visual cortex on visually guided l... more The effects of bilateral removal of the superior colliculus or visual cortex on visually guided locomotor movements in rats performing a brightness discrimination task were investigated directly with the use of cine film. Rats with collicular lesions showed patterns of locomotion comparable to or more efficient than those of normal animals when approaching one of 5 small doors located at one end of a large open area. In contrast, animals with large but incomplete lesions of visual cortex were distinctly impaired in their visual control of approach responses to the same stimuli. On the other hand, rats with collicular damage showed no orienting reflex or evidence of distraction in the same task when novel visual or auditory stimuli were presented. However, both normal and visual-decorticate rats showed various components of the orienting reflex and disturbance in task performance when the same novel stimuli were presented. These results suggest that although the superior colliculus does not appear to be essential to the visual control of locomotor orientation, this midbrain structure might participate in the mediation of shifts in visual fixation and attention. Visual cortex, while contributing to visuospatial guidance of locomotor movements, might not play a significant role in the control and integration of the orienting reflex.
American Journal of Public Health, 2003
Physiological Psychology, 1985
Applied psychology. Health and well-being, 2013
This paper reviews the history of the transition from the belief that gastrointestinal ulcers are... more This paper reviews the history of the transition from the belief that gastrointestinal ulcers are caused primarily by psychological factors to the current state of belief that they are caused primarily by infection and argues that neither is fully accurate. We argue that psychological factors play a significant role as predisposing to vulnerability, modulating of precipitation, and sustaining of gastric ulceration. We review data that challenge the assumption of a simple infectious disease model and adduce recent preclinical data that confirm the predisposing, modulatory, and sustaining roles for psychological factors. We note that others, too, are now challenging the adequacy of the contemporary simple bacterial infection model. We hope to replace the competition between psychology and medicine with cooperation in understanding and treating patients suffering gastric ulceration and ulcer.
Neuroscience & Biobehavioral Reviews, 1994
Since the publication of our initial review of restraint stress in 1986, much work has continued ... more Since the publication of our initial review of restraint stress in 1986, much work has continued with this technique, either as a tool for the investigation of other pharmacological, physiological, or pathologic phenomena or with restraint stress itself serving as the object of the study. As we noted in 1986, the major use of restraint has been for the induction of stress responses in animals and, more specifically, for the investigation of drug effects, particularly as they affect typical stress-related pathology--gastrointestinal, neuroendocrine, and immunological agents have been extensively studied. In compiling this update on restraint stress and its effects, we noted an increasing emphasis on central nervous system mechanisms in peripheral disease, especially gastrointestinal disease. In particular, many CNS-active agents have been tested for their effects on gastric and duodenal lesion formation and gastric secretion, including antidepressants, antipsychotics, anxiolytics, noradrenergic, serotonergic, dopaminergic, and peptidergic compounds. Some of these agents are especially active in the gastrointestinal tract even when administered centrally, further solidifying the concept of a brain-gut axis. The present update includes studies of: methods and procedures, pre-restraint manipulations, post-restraint/healing effects, and drug effects. In addition, a current bibliography of reports that have employed restraint is included.
Brain Research Reviews, 1991
ABSTRACT
Behavioral Neuroscience, 1991
Translational Psychiatry, 2016
Sexual abuse contributes to the development of multiple forms of psychopathology, including anxie... more Sexual abuse contributes to the development of multiple forms of psychopathology, including anxiety and depression, but the extent to which genetics contributes to these disorders among sexual abuse victims remains unclear. In this translational study, we first examined gene expression in the brains of rodents exposed to different early-life conditions (long, brief or no maternal separation). Hypothesizing that genes revealing changes in expression may have relevance for psychiatric symptoms later in life, we examined possible association of those genes with symptoms of anxiety and depression in a human sample of sexual abuse victims. Changes in rodent brain gene expression were evaluated by means of correspondence and significance analyses of microarrays by comparing brains of rodents exposed to different early-life conditions. Tag single-nucleotide polymorphisms (SNPs) of resulting candidate genes were genotyped and tested for their association with symptoms of anxiety and depress...
Scientific reports, Jan 27, 2017
Enzyme-linked immunosorbent assay (ELISA) kits are widely used to quantify corticosterone levels ... more Enzyme-linked immunosorbent assay (ELISA) kits are widely used to quantify corticosterone levels for the assessment of stress in laboratory animals. The aim of this experiment was simply to evaluate if four different and widely used commercial ELISA assays would yield the same or similar values of corticosterone in serum samples taken from laboratory rats after the mild stress of being held for sampling blood from the saphenous vein. Trunk blood was sampled from 32 male Wistar rats 30 minutes after this mild stress exposure and analysed with each of four commercial ELISA kits. Both the Arbor Assays and the DRG-4164 kits were significantly higher than the DRG-5186 and the Enzo kits. There were no significant differences between the DRG-5186 and Enzo kits. Overall the correlations between kits were high. In conclusion, the commercial ELISA kits tested in the present experiment yielded different values of total corticosterone in the same serum samples. The precision in determining true...
Journal of biological rhythms, 2016
Millions of people worldwide are working at times that overlap with the normal time for sleep. Sl... more Millions of people worldwide are working at times that overlap with the normal time for sleep. Sleep problems related to the work schedule may mediate the well-established relationship between shift work and increased risk for disease, occupational errors and accidents. Yet, our understanding of causality and the underlying mechanisms that explain this relationship is limited. We aimed to assess the consequences of night-shift work for sleep and to examine whether night-shift work-induced sleep disturbances may yield electrophysiological markers of impaired maintenance of the waking brain state. An experimental model developed in rats simulated a 4-day protocol of night-work in humans. Two groups of rats underwent 8-h sessions of enforced ambulation, either at the circadian time when the animal was physiologically primed for wakefulness (active-workers, mimicking day-shift) or for sleep (rest-workers, mimicking night-shift). The 4-day rest-work schedule induced a pronounced redistri...
Animal Models, Volume II, 2002
The open dentistry journal, 2015
Early life adverse events may influence susceptibility/resistance to chronic inflammatory disease... more Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. Compared to undisturbed controls, MD rats developed significantly more periodon...
Psychoneuroendocrinology, 2005
Proceedings of the National Academy of Sciences, 2002
The hippocampus has a critical role in several fundamental memory operations, including the condi... more The hippocampus has a critical role in several fundamental memory operations, including the conditioning of fear to contextual information. We show that the hippocampus is necessary also for unconditioned fear, and that the involved circuitry is at the ventral pole of the hippocampus. Rats with selective hippocampal lesions failed to avoid open arms in an elevated plus-maze and had decreased neuroendocrine stress responses during confinement to a brightly lit chamber. These effects were reproduced by lesions of the ventral half of the hippocampus, but not by damage to the dorsal three-quarters of the hippocampus or the amygdala. Ventral lesions failed to impair contextual fear conditioning or spatial navigation, suggesting that the ventral hippocampus may specifically influence some types of defensive fear-related behavior.
PLoS ONE, 2013
Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neur... more Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.
Physiology & Behavior, 2008
Social stressors play a major role in the pathogenesis of affective disorders like anxiety and de... more Social stressors play a major role in the pathogenesis of affective disorders like anxiety and depression. These disorders are associated with altered behaviour (i.e. locomotor activity, harm avoidance, startle response, anhedonia and sexual behaviour), sleep alterations and abnormalities in the stress response. The animal social defeat (SD) model is based on a natural conflict situation where a male intruder rat eventually subordinates itself to an unfamiliar territorial resident conspecific. The effects of defeat are studied in the intruder rat. The main purpose was to study the face validity of the SD model for affective disorders by investigating short-term and long-term consequences of single and/or double exposure to SD on behaviour and sleep in rats. In particular, the intention was to evaluate if SD could reproduce the alterations in locomotor activity, harm avoidance, startle response, anhedonia, sexual behaviour, stress responses and sleep parallel to those observed in patients with affective disorders. Social defeat induced low activity in the central sector of the open field (OF) (Paper I), indicating high harm avoidance which may reflect anxiety-like or depression-like behaviour. No short-term or long-term effects were seen on total locomotor activity in the OF (Papers I and II). Further, a lack of habituation to the OF across days was seen, which may reflect long-lasting heightened anxiety (Papers I and III). Overall, in the elevated plus maze (EPM) test, SD rats showed less total locomotor activity, less percentage time and less activity on the open arms, lasting up to 3 weeks after defeat (Paper II), possibly reflecting anxiety-like behaviours. High acoustic startle responses (ASR) were seen as a long-term effect of SD, probably reflecting an anxiety-like state (Paper II). A short-lasting reduced preference for sucrose was seen (Paper II), indicating an anhedonic state that may be interpreted as a transient anxiety-like symptom. Sexual behaviour was not affected (Paper I). As a group, SD rats did not show altered corticosterone responsiveness to OF exposure (Paper III). The SD rats showed a short-term increase in duration of slow wave sleep (SWS) 2 and sleep fragmentation (Paper I). Overall, SD rats did not show long-term effects on sleep or EEG power (Paper III). The effects of SD on sleep may be vii interpreted as anxiety, because they were short-lasting and the common sleep alterations seen in depression were not induced (e.g. reduced SWS2 and REM sleep alterations). A secondary aim was to compare effects of SD to the effects of inescapable footshock (IFS) (Paper II). The two stressors induced a similar short-term effect on sucrose preference and similar long-term anxiety-like behaviours in the EPM test. Contrary to what was expected, SD rats showed the highest ASR, while IFS rats showed the lowest total activity in the OF test. The results may reflect fundamental differences between SD and IFS. Another secondary aim was to explore the relationship between levels of corticosterone prior to SD or IFS stressor, and the different post-stressor behaviours (Paper II). Low pre-stress corticosterone level was expected to be associated with anxiety-like behaviours following stress. Overall, such a relationship was not found. Contrary to what was expected, the SD rats with high pre-stressor corticosterone level showed the greatest ASR, while IFS rats with low pre-stress corticosterone level did not show alterations in ASR. This further supports differences between the SD and the IFS stressor. The final secondary aim was to investigate differences in effects of SD on behaviour and sleep in two subgroups of rats with different coping styles in the SD (Paper III). Contrary to what was expected, rats fighting back in the SD confrontation showed longer latency to leave the start box, and spent less time in the OF arena compared to those not fighting back, indicating anxiety-like behaviour. They also showed more fragmentation of sleep in SWS1 and SWS2. The results may suggest that rapid submission during SD may be more adaptive than surrender after a longer fight, given these outcome measures. In conclusion, the studies presented in this thesis show that exposure to SD induced both short-term and long-term consequences for multiple behavioural features and at least short-term consequences for sleep. The behavioural consequences of SD are different from those of IFS. The studies generally support a high degree of face value for the SD model as a model for affective disorders, more relevant to anxiety than to depression. viii List of publications This thesis is based on the following papers.
Physiology & Behavior, 2004
In this study, we investigated the effects of three neonatal conditions on adult corticosterone (... more In this study, we investigated the effects of three neonatal conditions on adult corticosterone (CORT) levels, acoustic startle responses (ASRs), and vulnerability to colitis induced by dextran sulfate sodium (DSS) and how these early manipulations might interact with a brief stress exposure in adulthood on the same measures. Infant animals were subjected daily to either 180-min maternal separation [prolonged maternal separation (LMS)], 10-min maternal separation [brief maternal separation (BMS)], or nonhandling (NH) conditions during postnatal days 1-14. As adults, half of the animals were exposed to a series of 10 uncontrollable foot shocks. Animals were tested for CORT levels prior to and 10 days following shock/nonshock procedures before being tested for ASRs. Finally, all animals were exposed to 4% DSS in their drinking water for 6 days. LMS animals showed enhanced vulnerability to DSS-induced colitis when previously exposed to shock and enhanced stress reactivity responses as shown by elevated startle and CORT levels. Among the nonshocked animals, NH animals showed most colonic damage. Taken together, the results support previous findings suggesting that BMS has a protective effect on adult stress exposure. Additionally, BMS protects the animals from chemically induced colitis. The NH condition has clearly an effect on sensitizing mucosal response to DSS exposure.
Pharmacology Biochemistry and Behavior, 2006
Chronic stress is linked to development of depression and may trigger neurobiological changes und... more Chronic stress is linked to development of depression and may trigger neurobiological changes underlying the disease. Downregulation of the secretory peptide brain-derived neurotrophic factor (BDNF) and the transcriptional regulator calcium/cyclic-AMP responsive binding protein (CREB) have been implicated in stress and depression-related pathology in animal studies. When animals are exposed to the chronic mild stress (CMS) protocol, multiple depression-like symptoms are observed. Here we investigated the effect of CMS on BDNF protein expression and CREB activation in the dentate gyrus and hippocampus proper. Rats exposed for 5 weeks to repeated, unpredictable, mild stressors showed reduced BDNF expression and inhibited phosphorylation of CREB (Ser-133) in the dentate gyrus (-25.0%+/-3.5% and -29.7+/-7.3%, respectively), whereas no significant effects were observed in the hippocampus proper. CMS-treated rats consumed less sucrose compared to control rats, indicating a state of anhedonia. Moreover, phospho-CREB levels in the dentate gyrus were positively correlated with the animals' sucrose intake at the end of the CMS protocol. These results couple chronic mild stress to a downregulation of CREB activity and BDNF protein expression specifically within the dentate gyrus and support the possibility that the BDNF-CREB system plays an important role in the response to environmental challenges.
The European Journal of Orthodontics, 2009
The aim of the study was to investigate the effect of emotional stress on apical root resorption ... more The aim of the study was to investigate the effect of emotional stress on apical root resorption (ARR) and tooth displacement during orthodontic tooth movement in rats. A further area of interest was to evaluate if the expression of interleukin-1 alpha (IL-1a) as well as the density and distribution of peptidergic nerve fibres immunoreactive to calcitonin gene-related peptide (CGRP) in the periodontal ligament (PDL) are associated with possible stress-induced changes in root resorption and tooth movement. A total of 52 male Wistar rats, aged 6 weeks, were divided in three experimental and one control group (n = 4). Group 1 had orthodontic tooth movement and received foot shocks (OTMS; n = 16), group 2 had orthodontic tooth movement but received no foot shocks (OTMNS; n = 16), and group 3 had no orthodontic tooth movement and received foot shocks (NOTMS; n = 16). Each group was further divided into four subgroups (n = 4), corresponding to the period of the experiment, i.e. 3, 7, 13, and 21 days. At the end of each experimental period, the blood samples were taken, the animals were sacrificed, and the jaws excised, deminerialized, and processed for immunocytochemistry. One-way analysis of variance was used to detect inter-group differences for all investigated variables. CGRP immunopositive nerve fibres were evaluated qualitatively. All the experimental groups demonstrated higher corticosterone levels than the control group, suggesting a stress-induced experience by orthodontic treatment per se. The OTMS group had the least amount of cellular cementum throughout the experimental periods and showed significant reduction in tooth displacement, especially at 3 and 7 days. No obvious changes were observed in the dental tissue expression of IL-1a and CGRP immunoreactive nerve fibres between the stressed and non-stressed orthodontically treated groups.
Brain Research, 1975
The effects of bilateral removal of the superior colliculus or visual cortex on visually guided l... more The effects of bilateral removal of the superior colliculus or visual cortex on visually guided locomotor movements in rats performing a brightness discrimination task were investigated directly with the use of cine film. Rats with collicular lesions showed patterns of locomotion comparable to or more efficient than those of normal animals when approaching one of 5 small doors located at one end of a large open area. In contrast, animals with large but incomplete lesions of visual cortex were distinctly impaired in their visual control of approach responses to the same stimuli. On the other hand, rats with collicular damage showed no orienting reflex or evidence of distraction in the same task when novel visual or auditory stimuli were presented. However, both normal and visual-decorticate rats showed various components of the orienting reflex and disturbance in task performance when the same novel stimuli were presented. These results suggest that although the superior colliculus does not appear to be essential to the visual control of locomotor orientation, this midbrain structure might participate in the mediation of shifts in visual fixation and attention. Visual cortex, while contributing to visuospatial guidance of locomotor movements, might not play a significant role in the control and integration of the orienting reflex.
American Journal of Public Health, 2003
Physiological Psychology, 1985
Applied psychology. Health and well-being, 2013
This paper reviews the history of the transition from the belief that gastrointestinal ulcers are... more This paper reviews the history of the transition from the belief that gastrointestinal ulcers are caused primarily by psychological factors to the current state of belief that they are caused primarily by infection and argues that neither is fully accurate. We argue that psychological factors play a significant role as predisposing to vulnerability, modulating of precipitation, and sustaining of gastric ulceration. We review data that challenge the assumption of a simple infectious disease model and adduce recent preclinical data that confirm the predisposing, modulatory, and sustaining roles for psychological factors. We note that others, too, are now challenging the adequacy of the contemporary simple bacterial infection model. We hope to replace the competition between psychology and medicine with cooperation in understanding and treating patients suffering gastric ulceration and ulcer.
Neuroscience & Biobehavioral Reviews, 1994
Since the publication of our initial review of restraint stress in 1986, much work has continued ... more Since the publication of our initial review of restraint stress in 1986, much work has continued with this technique, either as a tool for the investigation of other pharmacological, physiological, or pathologic phenomena or with restraint stress itself serving as the object of the study. As we noted in 1986, the major use of restraint has been for the induction of stress responses in animals and, more specifically, for the investigation of drug effects, particularly as they affect typical stress-related pathology--gastrointestinal, neuroendocrine, and immunological agents have been extensively studied. In compiling this update on restraint stress and its effects, we noted an increasing emphasis on central nervous system mechanisms in peripheral disease, especially gastrointestinal disease. In particular, many CNS-active agents have been tested for their effects on gastric and duodenal lesion formation and gastric secretion, including antidepressants, antipsychotics, anxiolytics, noradrenergic, serotonergic, dopaminergic, and peptidergic compounds. Some of these agents are especially active in the gastrointestinal tract even when administered centrally, further solidifying the concept of a brain-gut axis. The present update includes studies of: methods and procedures, pre-restraint manipulations, post-restraint/healing effects, and drug effects. In addition, a current bibliography of reports that have employed restraint is included.
Brain Research Reviews, 1991
ABSTRACT
Behavioral Neuroscience, 1991