Hypothalamic self-stimulation in rats following immunosympathectomy or central nerve growth factor antiserum injection.

In Experiment 1, immunosympathectomized rats self-stimulated at a much lower rate on high variable ratio schedules of reinforcement than injected controls. No differences were found for responding on continuous reinforcement or low variable ratio reinforcement schedules. In Experiment 2, a similar reduction in varialbe ratio response rate was found for subjects centrally injected with nerve growth factor-antiserum relative to controls. The results suggest a reduction in central catecholamine levels as a result of antiserum treatment.     

Behavior of rats following a stress situation

The Psychological Record -     

Sex differences in chronic stress effects on memory in rats

Recent studies in rodent models and in humans have shown that the status of both the gonadal and adrenal axes (hypothalamic-pituitary-gonadal, HPG and hypothalamic-pituitary-adrenal, HPA, respectively) can influence learning and memory function. In this article, the effects of activating the HPA axis (stress) on performance of memory tasks in rats are reviewed. More importantly, results are presented which show that chronic stress has a different impact on performance of these tasks depending upon the sex of the rat. These observations are novel and potentially important since few studies, animal or human, have utilized females as subjects in studies of the stress response. Sex differences in the effects of chronic stress on memory were investigated in rats using an object recognition task and two spatial memory tasks, radial arm maze and object location. Given the same chronic stress--21 days of restraint for 6 h each day--males were impaired in all of the memory tests while females showed enhanced performance of the spatial memory tasks and no changes in object recognition performance. Levels of neurotransmitters and metabolites were measured in brain areas important for cognition in the subjects in order to determine neural systems that may respond to stress and mediate the cognitive responses. These results show that responses of monoamine and amino acid containing neural systems may contribute to or underlie sex differences in stress effects on cognition. Stress decreased dopaminergic activity in the frontal cortex and amygdala of males but not females; whereas, in CA3 of the hippocampus, stress increased levels of 5-HT and norepinephrine in females, but not males, and increased GABA in males, but not females. Finally, a possible role for estradiol in mediating sexually differentiated responses to stress was examined. Behavioral and neurochemical evaluations in ovariectomized, stressed females, with or without estrogen replacement, suggest that sex differences in response to stress are influenced by both the organizing and activating effects of estradiol. A few, recent studies in humans, that show sexually dimorphic relationships between chronic stress and cognition, are also highlighted. These results in humans are consistent with the pattern of results in rats. Clearly, further studies are necessary to substantiate sex differences in stress effects on memory function in humans and to understand mechanisms whereby estrogen may influence the stress response in rats. Nonetheless, recent studies show sexually differentiated cognitive responses to chronic stress and underline the importance of considering the sex/gender of subjects when studying the stress response.     

Directed forgetting following mood induction in chronic posttraumatic stress disorder patients

Current research of posttrauma sequelae suggests that intrusive rather than avoidant-dissociative models more accurately represent the encoding processes of trauma cues. However, posttraumatic stress disorder (PTSD) is often conceptualized as a phasic phenomenon, altering between arousal and avoidance states. The failure to support a relationship between avoidant encoding style and PTSD may reflect this alteration. To explore this hypothesis, participants with PTSD and controls (no PTSD) completed an item-cued directed-forgetting task, following either a dissociative or a serenity (control) mood induction. Results suggested that, following the serenity induction, a standard directed-forgetting effect was observed. However, following the dissociation induction, this effect was not observed. The role of dissociation in impairing encoding via lack of selective rehearsal or source discrimination is discussed.     

Adaptation of anterior pituitary hormones to chronic noise stress in male rats

We have studied the effects of acute and chronic noise on serum levels of pituitary hormones in male Wistar rats. Acute noise increased serum levels of corticosterone, prolactin, and luteinizing hormone and decreased serum GH. FSH was unaffected by this stressor. Chronic noise did not modify basal levels of any hormone studied, however responsiveness of some hormones to the same stimuli was altered. Reduced corticosterone, prolactin, and GH responses to noise was observed after previous chronic exposure to this stimuli. LH response followed the same pattern although it did not reach statistical significance. It might be concluded that adaptation to a repeated stress stimulus is not confined to the pituitary-adrenal axis, however, the degree of adaptation could vary between different hormones.     

A genetic analysis of stereotypy in the mouse: dopaminergic plasticity following chronic stress

After repeated stressful experiences, DBA/2 (DBA) mice showed an increase in apomorphine-induced climbing while C57BL/6 (C57) mice showed a clear-cut decrease of this behavior. Genetic analysis involving F1 and F2 hybrids and the backcross populations (F1 X C57; F1 X DBA) indicated complete dominance of the C57 genotype and a significant genotype X environment interaction. These findings are discussed in terms of dopaminergic plasticity and of the heuristic value of this animal model in relation to disturbed behaviors triggered by stressful experiences.     

Influence of housing on the consequences of chronic mild stress in female rats

The chronic mild stress (CMS) paradigm was developed to model anhedonia in animals. The repeated administration of a series of unpredictable, mild stressors attempts to mimic the daily stress associated with the onset of clinical depression in humans. Male animals are predominantly used in these investigations despite significant, well-documented sex differences in human depression. In this study, the CMS procedure was modified to be more ecologically relevant to female animals. The effects of stress on sucrose preference, social interaction, rate of weight gain, and regularity of the estrous cycle in female Sprague-Dawley (SD) rats were evaluated in both single- and paired-housed rats, during 3 weeks each of baseline, CMS, and post-CMS phases. The results indicate that only single-housed rats exposed to stressors have a reduced rate of weight gain, significantly attenuated sucrose preference levels, and increased social interaction scores during the CMS phase of the study. Housing condition more than exposure to stress appeared to contribute to the disruption of estrous cycling in some animals. These data suggest that housing affords some protection from the negative consequences of CMS, at least in female rats, and that lack of social interaction in the single-housing condition may render females more vulnerable to stress-related illnesses. The development of paradigms that model human depression should emphasize sex-specific differences.     

Gender differences in acute and chronic stress in Wistar Kyoto (WKY) rats

While females are considered more susceptible to depressive behavior, this assertion is not strongly supported by the experimental literature. Since stress contributes to depressive behavior, male and female Wistar Kyoto (WKY) rats were exposed to either one session (acute stress) or 5 sessions (chronic stress) of restraint plus cold in order to study depressive behavior in male and female rats. After their respective treatment exposure, rats were tested in the open field test (OFT) and for retention of a passive-avoidance (P-A) task. One stress session resulted in significant immobility in the OFT for males, whereas 5 sessions were required to produce similar immobility in female rats. Acute stress interfered with the retention of the P-A response for males, while both acute and chronic stress produced poor P-A responses in female rats. Food consumption decresed, progressively, as a function of stress sessions, in female rats, whereas feeding in males returned to control levels after five stress days. Both acute and chronic stress exacerbated the stress ulcer response in male rats, but not in female rats. Chronic, but not acute, stress resulted in an increase in serotonin transporter mRNA levels in the dorsal raphe nucleus of both male and, female rats. The general consensus from these data suggested that female rats were more vulnerable to chronic stress and consequently supported the notion that females may be more susceptible to stress induced behavioral depression.     

Effects of chronic social stress during lactation on maternal behavior and growth in rats

Maternal mood disorders such as depression and chronic anxiety can negatively affect the lives of not only mothers, but also of partners, offspring, and future generations. Chronic exposure to psychosocial stress is common in postpartum mothers, and one of the strongest predictors of postpartum depression is social conflict. The objective of the current study was to evaluate the effects of chronic social stress (CSS) during lactation on the maternal behavior (which consists of maternal care and aggression toward a novel conspecific) of lactating rats, as well as on the growth of the dams and their offspring. It was hypothesized that chronic daily exposure to a novel male intruder would alter the display of maternal behavior and impair growth in both the dam and offspring during lactation due to the potentially disruptive effects on maternal behavior and/or lactation. The data indicate that CSS during lactation attenuates maternal care and the growth of both dams and pups, and increases self-grooming and maternal aggression toward a novel male intruder. These results support the use of CSS as a relevant model for disorders that impair maternal behavior and attenuate growth of the offspring, such as postpartum depression and anxiety.     

Hippocampal low-frequency stimulation and chronic mild stress similarly disrupt fear extinction memory in rats

Disruptions of fear extinction-related potentiation of synaptic efficacy in the connection between the hippocampus (HPC) and the medial prefrontal cortex (mPFC) have been shown to impair the recall of extinction memory. This study was undertaken to examine if chronic mild stress (CMS), which is known to alter induction of HPC–mPFC long-term potentiation, would also interfere with both extinction-related HPC–mPFC potentiation and extinction memory. Following fear conditioning (5 tone-shock pairings), rats were submitted to fear extinction (20 tone-alone presentations), which produced an increase in the amplitude of HPC–mPFC field potentials. HPC low-frequency stimulation (LFS), applied immediately after training, suppressed these changes and induced fear return during the retention test (5 tone-alone presentations). CMS, delivered before fear conditioning, did not interfere with fear extinction but blocked the development of extinction-related potentiation in the HPC–mPFC pathway and impaired the recall of extinction. These findings suggest that HPC LFS may provoke metaplastic changes in HPC outputs that may mimic alterations associated with a history of chronic stress.     

Gender differences in acute and chronic stress in Wistar Kyoto (WKY) rats.

While females are considered more susceptible to depressive behavior, this assertion is not strongly supported by the experimental literature. Since stress contributes to depressive behavior, male and female Wistar Kyoto (WKY) rats were exposed to either one session (acute stress) or 5 sessions (chronic stress) of restraint plus cold in order to study depressive behavior in male and female rats. After their respective treatment exposure, rats were tested in the open field test (OFT) and for retention of a passive-avoidance (P-A) task. One stress session resulted in significant immobility in the OFT for males, whereas 5 sessions were required to produce similar immobility in female rats. Acute stress interfered with the retention of the P-A response for males, while both acute and chronic stress produced poor P-A responses in female rats. Food consumption decreased progressively, as a function of stress sessions, in female rats, whereas feeding in males returned to control levels after five stress days. Both acute and chronic stress exacerbated the stress ulcer response in male rats, but not in female rats. Chronic, but not acute, stress resulted in an increase in serotonin transporter mRNA levels in the dorsal raphe nucleus of both male and female rats. The general consensus from these data suggested that female rats were more vulnerable to chronic stress and consequently supported the notion that females may be more susceptible to stress-induced behavioral depression. Key Words: WKY rats, acute and chronic stress, gender, passive avoidance, open field behavior, stress-ulcer, adrenal weight, serotonin, dorsal raphe nucleus     

Effect of chronic cold stress on intestinal epithelial cell proliferation and inflammation in rats

The present study evaluated the effect of chronic cold stress on intestinal epithelial cell proliferation and inflammation. Male Wistar rats were subjected to cold exposure for three weeks. At the end of the cold exposure, intestinal cell proliferation, luminal nitrite and protein levels, intestinal myeloperoxidase activity and mast cell numbers were evaluated. Severely compromised proliferation rate of the crypt-base cells was observed under chronic stress conditions. Cells isolated from stressed rats showed a decreased DNA content in villus and lower villus cell fractions and an increased DNA content in the crypt cells, as compared to controls. Chronic cold stress resulted in increased luminal nitrite, luminal protein levels, and intestinal myeloperoxidase activity. The number of mast cells was significantly elevated under chronic stress conditions. Chronic cold stress resulted in a compromised intestinal epithelial cell proliferation rate and induced inflammation in the rat small intestine, through the combined action of nitric oxide, neutrophils and mast cells.     

Forced treadmill exercise prevents oxidative stress and memory deficits following chronic cerebral hypoperfusion in the rat

Physical activity impacts functional recovery following stroke in humans, however its effects in experimental animals submitted to chronic cerebral hypoperfusion have not been investigated. The aim of this study was to evaluate the therapeutic potential of exercise, as assessed by cognitive activity in the Morris water maze and the brain oxidative status, through measurement of macromolecules damage, TBARS levels and total cellular thiols, as well as antioxidant enzymes in hippocampus, striatum and cerebral cortex. Adult male Wistar rats were submitted to the modified permanent bilateral occlusion of the common carotid arteries (2VO) method, with right common carotid artery being first occluded, and tested 3 months after the ischemic event. The effects of three different exercise protocols were examined: pre-ischemia, post-ischemia and pre+post-ischemia. Physical exercise consisted of sessions of 20-min, 3 times per week during 12 weeks (moderate intensity). Rats were submitted to cognitive assessment, in both reference and working spatial memory and after the last testing session were sacrificed to have oxidative stress parameters determined. Hypoperfusion caused a significant cognitive deficit in both spatial water maze tasks and this effect was reversed in rats receiving exercise protocol post and pre+post the ischemic event. Moreover, forced regular treadmill exercise regulated oxidative damage and antioxidant enzyme activity in the hippocampus. These results suggest that physical exercise protects against cognitive and biochemical impairments caused by chronic cerebral hypoperfusion.     

Hypothalamic and hippocampal release of serotonin in rats bred for hyper- or hypo-anxiety

Microdialysis for measurement of serotonin in the paraventricular nucleus of the hypothalamus (PVN) and the dorsal hippocampus was performed under both basal and stimulated conditions, known to elicit differential behavioral and neuroendocrine responses in rats with inborn high (HAB) or low (LAB) anxiety-related behavior. We studied the release of hypothalamic and hippocampal serotonin in response to elevated platform exposure and forced swim stress, a mild emotional and a combined emotional and physical stressor, respectively. The data suggest that serotonin release patterns may depend on the inborn level of anxiety, the brain area dialyzed, and the stressor the animals were exposed to. Under basal conditions, no differences in serotonin release in either the PVN or dorsal hippocampus were observed between HAB and LAB rats. While in the PVN open platform exposure failed to change the release of serotonin, forced swim stress induced an increase in both HAB (p = 0.0001) and LAB (p = 0.01) rats with a significantly greater effect in the former (p = 0.027). In the dorsal hippocampus, only LABs, but not HABs, responded to the elevated platform exposure by enhancing the release of serotonin (p = 0.01). Also, forced swim stress increased hippocampal serotonin only in LAB (p = 0.002), but not HAB, rats probably indicating an involvement of hippocampal serotonin in locomotion and active stress coping. It remains to be shown to what extent the differences in serotonin release contribute to neuroendocrine and behavioral differences between HAB and LAB rats.