Pharmacological suppression of corticosterone secretion in response to a physical stressor does not prevent the delayed persistent increase in circulating basal corticosterone concentration

Elevated basal plasma corticosterone concentrations have been observed for several days after the cessation of severe stress. In the present study, we examined whether or not the acute plasma corticosterone response to stress is necessary to elicit increased basal plasma corticosterone concentrations the following day. Pretreatment with metyrapone (100 m a g , intraperitoneal)1 h before inescapable stress (40 2mA tail shocks delivered over a 1-h period) (IS)blocked the acute plasma corticosterone response to IS. However, elevated basal plasma corticosterone concentrations still emerged the next day. These results suggest that the corticosterone response to stress, and its attendant feedback, are not necessary to produce persistent hypothalamic-pituitary-adrenal axis (HPAA) activation.     

Reliability of the Chronic Mild Stress paradigm: Implications for research and animal welfare

The Chronic Mild Stress (CMS) model for depression has become central to the empirical literature on depression. There are however inconsistencies in the literature concerning the robustness of the phenomenon of anhedonia following CMS procedures. We report that not only did our procedures (modeled on the original reports) fail to induce an anhedonia, but in fact led to increased sucrose consumption. Furthermore, corticosterone levels following CMS procedures were lower than following control procedures. Given that this is not the first report of such findings, it is important to evaluate whether and which aspects of the experimental methodology are necessary or sufficient to induce the state of anhedonia.     

Memory enhancement of classical fear conditioning by post-training injections of corticosterone in rats

There is extensive evidence that post-training administration of the adrenocortical hormone corticosterone facilitates memory consolidation processes in a variety of contextual and spatial-dependent learning situations. The present experiments examine whether corticosterone can modulate memory of auditory-cue classical fear conditioning, a learning task that is not contingent on contextual or spatial representations. Male Sprague-Dawley rats received three pairings of a single-frequency auditory stimulus and footshock, followed immediately by a post-training subcutaneous injection of either corticosterone (1.0 or 3.0mg/kg) or vehicle. Retention was tested 24h later in a novel test chamber and suppression of ongoing motor behavior served as the measure of conditioned fear. Corticosterone dose-dependently facilitated suppression of motor activity during the 10-s presentation of the auditory cue. As corticosterone administration did not alter responding after unpaired presentations of tone and shock, tone alone, shock alone or absence of tone/shock, the findings indicated that corticosterone selectively facilitated memory of the tone-shock association. Furthermore, injections of corticosterone given 3h after training did not alter motor activity during retention testing, demonstrating that corticosterone enhanced time-dependent memory consolidation processes. These findings provide evidence that corticosterone modulates the consolidation of memory for auditory-cue classical fear conditioning and are consistent with a wealth of data indicating that glucocorticoids can modulate a wide variety of emotionally influenced memories.     

Methods for averaging alpha coefficients in reliability generalization studies

The reliability generalization (RG) approach is a kind of meta-analysis that aims to statistically integrate a set of independent reliability coefficients obtained in several applications of a test, with the purpose of characterizing the measurement error and determining which factors related to the studies and samples can explain its variability. Diverse procedures have been proposed in the literature for averaging a set of independent alpha coefficients, and there is no consensus about which methods are best. Here, we present the results of a Monte Carlo simulation study, comparing the performance of twelve procedures proposed in Feldt and Charter, in terms of bias and mean square error. These procedures differ from each other in the transformation (or not) of the coefficients, and in the application or not of a weighting scheme based on sample size. Our results recommend using weighted methods in contrast to unweighted ones, and transforming the coefficients by the Hakstian and Whalen's proposal or by the proposal based on the square root of the inverse alpha coefficient. Lastly, we discuss the relations between the diverse procedures for averaging alpha coefficients with fixed-effects, random-effects, and varying coefficients models.     

Effects of motherless rearing on basal and stress-induced corticosterone secretion in rat pups

Rearing of rat pups without a mother, artificial rearing (AR), produces substantial changes in the pups' behavior in later life. These changes are similar to those produced by the stress of repeated mother-pup separations. The predominant interpretation is that the long-term effects of disruptions to the mother-pup relationship are mediated by exposure to elevated levels of corticosterone which affect the development of neurobiological systems underlying cognition and behavior. Indeed, repeated separation of pups from the mother sensitizes the pups' corticosterone response to stress. This study examined basal and stress-induced corticosterone release in AR pups. Corticosterone levels were increased immediately following implantation of feeding cannulae. One day after the start of AR, circulating concentrations of corticosterone were not increased unless AR pups were challenged with an additional stressor (injection). Corticosterone levels were lowest when cannulation and AR started on postnatal day (PND) 5 compared with earlier PNDs. On PND 12, there was no evidence of increased corticosterone levels in AR pups at baseline or in response to stress, indicating that AR did not result in persistent sensitization of corticosterone release. The long-term effects of motherless rearing on rat behavior are mediated by mechanisms that are independent of sustained early corticosterone exposure.     

Glucocorticoids enhance taste aversion memory via actions in the insular cortex and basolateral amygdala

It is well established that glucocorticoid hormones strengthen the consolidation of hippocampus-dependent spatial and contextual memory. The present experiments investigated glucocorticoid effects on the long-term formation of conditioned taste aversion (CTA), an associative learning task that does not depend critically on hippocampal function. Corticosterone (1.0 or 3.0 mg/kg) administered subcutaneously to male Sprague–Dawley rats immediately after the pairing of saccharin consumption with the visceral malaise-inducing agent lithium chloride (LiCl) dose-dependently increased aversion to the saccharin taste on a 96-h retention test trial. In a second experiment, rats received corticosterone either immediately after saccharin consumption or after the LiCl injection, when both stimuli were separated by a 3-h time interval, to investigate whether corticosterone enhances memory of the gustatory or visceral stimulus presentation. Consistent with the finding that the LiCl injection, but not saccharin consumption, increases endogenous corticosterone levels, corticosterone selectively enhanced CTA memory when administered after the LiCl injection. Suppression of this training-induced release of corticosterone with the synthesis-inhibitor metyrapone (35 mg/kg) impaired CTA memory, and was dose-dependently reversed by post-training supplementation of corticosterone. Moreover, direct post-training infusions of corticosterone into the insular cortex or basolateral complex of the amygdala, two brain regions that are critically involved in the acquisition and consolidation of CTA, also enhanced CTA retention, whereas post-training infusions into the dorsal hippocampus were ineffective. These findings provide evidence that glucocorticoid effects on memory consolidation are not limited to hippocampus-dependent spatial/contextual information, but that these hormones also modulate memory consolidation of discrete-cue associative learning via actions in other brain regions.     

Long-term effects of footshock and social defeat on anxiety-like behaviours in rats: Relationships to pre-stressor plasma corticosterone concentration

We compared the consequences of two stressors, 'unnatural' inescapable footshocks (IFSs) and 'natural' social defeat (SD), on behaviours typically sensitive to stress [sucrose preference, open field (OF), elevated plus maze (EPM) and acoustic startle responses (ASRs)] and the association with pre-stressor plasma corticosterone concentration. After initial blood sampling, rats (n?=?20 per group) were exposed to either 10 IFSs (1?mA intensity, 5?s duration each) or to 1?h SD (defeat by an aggressive resident male rat and further exposure but separated in a small cage) or to control procedures (handling). Rats were tested once for ASR (day 19), while the other behavioural tests were applied once weekly for 3 weeks. Both stress groups showed short-lasting lowered sucrose preference, and in the EPM they showed shorter total distance moved, shorter distance moved on open arms and less time on open arms compared to controls. In the OF test, IFS rats showed shorter total distance moved up to 2 weeks after stress. The SD group showed shorter total distance moved in the OF, which was only significant 2 weeks after stress. Low pre-stressor plasma corticosterone concentration was only associated with defecation (IFS rats) and latency to enter open arms in the EPM (all low corticosterone subgroups, n?=?10 per subgroup). SD rats with high initial plasma corticosterone concentration showed enhanced ASR compared to the other subgroups with high initial plasma corticosterone concentration (n?=?9 per subgroup). The results indicate that footshock and SD, while generally leading to an increase in anxiety behaviours, represent qualitatively different stressors.     

Risk assessment behaviors associated with corticosterone trigger the defense reaction to social isolation in rats: role of the anterior cingulate cortex

The extent to which the hypothalamic-pituitary-adrenal axis is activated by short-term and long-term consequences of stress is still open to investigation. This study aimed to determine (i) the correlation between plasma corticosterone and exploratory behavior exhibited by rats subjected to the elevated plus maze (EPM) following different periods of social isolation, (ii) the effects of the corticosterone synthesis blocker, metyrapone, on the behavioral consequences of isolation, and (iii) whether corticosterone produces its effects through an action on the anterior cingulate cortex, area 1 (Cg1). Rats were subjected to 30-min, 2-h, 24-h, or 7-day isolation periods before EPM exposure and plasma corticosterone assessments. Isolation for longer periods of time produced greater anxiogenic-like effects on the EPM. However, stretched attend posture (SAP) and plasma corticosterone concentrations were increased significantly after 30?min of isolation. Among all of the behavioral categories measured in the EPM, only SAP positively correlated with plasma corticosterone. Metyrapone injected prior to the 24?h isolation period reversed the anxiogenic effects of isolation. Moreover, corticosterone injected into the Cg1 produced a selective increase in SAP. These findings indicate that risk assessment behavior induced by the action of corticosterone on Cg1 neurons initiates a cascade of defensive responses during exposure to stressors.     

Timing is essential for rapid effects of corticosterone on synaptic potentiation in the mouse hippocampus

Stress facilitates memory formation, but only when the stressor is closely linked to the learning context. These effects are, at least in part, mediated by corticosteroid hormones. Here we demonstrate that corticosterone rapidly facilitates synaptic potentiation in the mouse hippocampal CA1 area when high levels of the hormone and high-frequency stimulation coincide in time, but not when corticosterone is given either before or after repetitive stimulation. This effect could not be blocked by antagonists of the mineralocorticoid receptor and glucocorticoid receptor (spironolactone and RU 38486, respectively). These data provide a biological substrate for the important behavioral observation that stress and corticosteroid hormones can facilitate learning and memory processes.     

Support for a bimodal role for type II adrenal steroid receptors in spatial memory.

We investigated the effects of acute adrenal steroid treatment on spatial memory using the Y-maze and employing adrenal steroid receptor antagonists and agonists. For receptor activation, adrenalectomized rats were injected 2 h prior to their first Y-maze trial with sesame oil (adrenalectomy or SHAM), stress levels of corticosterone, a Type I receptor agonist (aldosterone), or a Type II receptor agonist (RU362). For receptor inactivation, unoperated rats were injected with a Type I receptor antagonist (RU318), a Type II receptor antagonist (RU555), sesame oil, or not injected at all. The findings indicated that spatial memory was impaired when the Type II receptors were blocked (RU555) or highly occupied (corticosterone or RU362) and normal for the other treatment conditions. These data suggest that the Type II receptors may be responsible for the inverted U-shaped relationship between spatial memory and corticosterone levels reported by others.     

Salivary Cortisol as a Biomarker in Social Science Research

Cortisol, a neuroendocrine hormone measurable in saliva, responds to internal and external triggers. In providing a peripheral ‘window on the brain’, it has been increasingly incorporated into social psychological studies. Cortisol secretion can be studied in two main ways, examination of acute stress reactivity and examination of the basal circadian patterns. These can inform aspects of acute and chronic stress exposure and relationships with health. Within non‐clinical populations, cortisol effects are largely driven by differences in the perception of threat. For social psychologists, this provides an interesting avenue for the investigation of social factors that mediate perceptions of threat, such as social support, relationship processes, and group dynamics in acute and chronic stress. This paper provides a background to understanding the regulation and function of cortisol, and issues arising in relation to its measurement in saliva. It discusses and makes recommendations on the use of appropriate cortisol measures in the study of both acute and chronic stress. Used and interpreted appropriately, stress reactivity and basal ambulatory measures of salivary cortisol can provide a valuable adjunct to self‐report and observation in social psychological research. © 2013 John Wiley & Sons Ltd     

Post-training administration of corticosterone enhances consolidation of contextual fear memory and hippocampal long-term potentiation in rats

This study was designed to examine the effect of corticosterone on consolidation of contextual fear memory and hippocampal long-term potentiation (LTP) in rats. In Experiment 1, dose–response effects of corticosterone on consolidation of contextual fear memory were determined. Immediately after training in contextual fear conditioning task, rats received different doses of corticosterone. Testing 24 h later, it revealed that corticosterone enhanced memory consolidation in an inverted U shape as evidenced in increased freezing behavior of corticosterone-treated animals. The most effective dose was 3 mg/kg. In Experiment 2, LTP was examined in rats whose memory consolidation has been enhanced with corticosterone. The rats were trained as the above and received corticosterone (3 mg/kg) immediately after training. Immediately or up to one day after retention test, rats were anesthetized with urethane for LTP experiments. For LTP induction, three episodes of high frequency stimuli, 30 s apart, were delivered to the perforant path, each consisting of 10 stimuli at 250 Hz. LTP was assessed by measuring the increase in the initial slope of the population excitatory post-synaptic potentials and the amplitude of the population spikes. Data indicated that animals whose memory has been enhanced by corticosterone, also displayed enhanced hippocampal LTP. The above findings suggest that glucocorticoids may enhance contextual fear memory consolidation via enhancing hippocampal LTP.     

Neurotoxicity of Kainate to the Hippocampus is not Accrued by Aging, Stress and Exogenous Corticosterone in Wistar Kyoto and Spontaneously Hypertensive Rats

It has been reported that a high corticosterone milieu can exacerbate various experimental insults to the nervous system, in particular to the hippocampus. However, in many of these studies the above milieu was attained by injecting corticosterone in doses (e.g. 10 mg/rat) producing supraphysiological concentrations. In the present study we have investigated whether high plasma corticosterone levels, such as those associated with aging or stress, potentiate a hippocampal excitotoxic insult. Male Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR) at the age of 6, 12, 18 and 24 months (only WKY for the oldest age) were used. As in other strains, aging in these rats was marked by an increase in basal plasma corticosterone levels. Rats were infused in the dorsal hippocampus with kainic acid (0.035 μg/hippocampus) and the neuronal injury was evaluated within the areas CA3 and CA4. Results indicated that neither aging nor the hypertensive condition affected kainic acid neurotoxicity. In order to study the effect of stress, rats were stressed twice a day, with alternate types of stressors to avoid possible habituation, 3 days prior to and 3 days following the kainic acid infusion. Using this experimental paradigm the hippocampal damage in stressed rats was of the same degree as in non-stressed controls. In a complementary set of experiments, 6 month old WKY and SHR rats were injected with corticosterone (10 mg/rat s.c.). Four hours after administration plasma corticosterone levels in the range of 60-70 μg/100 ml were found. Moreover, a time-course study showed a plasma corticosterone peak in the range of 240 μg/100 ml. Daily corticosterone administration for 3 days before and 3 days after kainic acid infusion potentiated the hippocampal damage in 6 months old SHR but not in the WKY. These results demonstrate that elevation of corticosterone levels within physiological range does not exacerbate hippocampal kainate neurotoxicity and that pharmacological doses of glucocorticoid hormone, which produces plasma levels well above those observable in any physiopathological condition, might, with some strain dependency, potentiate a hippocampal neurotoxic insult.     

Glucocorticoids, the hippocampus, and behavior: interactive relation between task activation and steroid hormone binding specificity

A previous investigation established a modulatory effect of adrenal glucocorticoids on a behavior generally believed to require participation of the hippocampus for normal expression. For further delineation of whether the observed effects on appetitive extinction are consistent with a glucocorticoid action on hippocampus, adrenalectomized rats were administered either corticosterone or dexamethasone, a synthetic glucocorticoid that is accumulated much less intensively by the hippocampus than is corticosterone. While corticosterone normalized extinction, dexamethasone did not. In two other hippocampal-dependent behaviors, alternation and exploration, there was no glucocorticoid modulation of behavior, which may indicate that factors such as the level of activation of the type of learning determine whether a glucocorticoid effect will occur. These findings of a glucocorticoid action on one of three tasks that involve hippocampal function reinforce the notion that in addition to their well-studied actions in protein and carbohydrate metabolism, the adrenal glucocorticoids may also be subtle modulators of behavior.     

Administration of corticosterone after memory reactivation disrupts subsequent retrieval of a contextual conditioned fear memory: dependence upon training intensity

Reactivation of stabilized memories returns them to a labile state and causes them to undergo extinction or reconsolidation processes. Although it is well established that administration of glucocorticoids after training enhance consolidation of contextual fear memories, but their effects on post-retrieval processes are not known. In this study, we first asked whether administration of corticosterone after memory reactivation would modulate subsequent expression of memory in rats. Additionally, we examined whether this modulatory action would depend upon the strength of the memory. We also tested the effect of propranolol after memory reactivation. Adult male Wistar rats were trained in a fear conditioning system using moderate (0.4 mA) or high shock (1.5 mA) intensities. For reactivation, rats were returned to the chamber for 90 s 24h later. Immediately after reactivation, rats were injected with corticosterone (1, 3 or 10mg/kg) or vehicle. One, 7 and 14 days after memory reactivation, rats were returned to the context for 5 min, and freezing behavior was scored. The findings indicated that corticosterone when injected after memory reactivation had no significant effect on recall of a moderate memory, but it impaired recall of a strong memory at a dose of 3mg/kg. Propranolol (5mg/kg) given after the reactivation treatment produced a modest impairment that persisted over three test sessions. Further, the results showed that corticosterone, but not propranolol deficit was reversed by a reminder shock. These findings provide evidence that administration of glucocorticoids following memory reactivation reduces subsequent retrieval of strong, but not moderate, contextual conditioned fear memory likely via acceleration of memory extinction. On the other hand, propranolol-induced amnesia may result from blockade of reconsolidation process. Further studies are needed to determine the underlying mechanisms.     

Cholinergic Responsiveness of Rat CA1 Hippocampal Neurons In Vitro: Modulation by Corticosterone and Stress

Corticosterone can activate two corticosteroid receptor types in rat hippocampus: low doses activate mineralocorticoid receptors (MR) while high doses additionally activate glucocorticoid receptors (GR). We found that corticosterone, administered to adrenalectomized rats in vivo, dose-dependently modulates carbachol responsiveness of CA1 hippocampal neurons, recorded subsequently in vitro. Thus, the carbachol (3 μM) induced membrane depolarization in CA1 neurons was relatively large in hippocampal slices where either (almost) no corticosteroid receptors were activated (0-1 μg corticosterone/100g body weight) or where both MRs and GRs were occupied by high corticosterone doses (100-1000 μg/100g). Slices from rats that received intermediate doses of corticosterone (10-30 μg/100g) resulting in predominant MR occupation, displayed significantly suppressed carbachol responses. In adrenally intact rats with MRs and GRs fully activated by a very high dose of corticosterone (1 mg/100g), carbachol responses were increased compared to rats that received only the vehicle or that were untreated. When endogenous corticosterone levels were elevated by ether stress, carbachol responses were not increased. These findings suggest that a shift in the relative occupation of MRs and GRs occurring under physiological conditions is associated with modulation of acetylcholine sensitivity in CA1 neurons. After stress, however, the sensitivity to acetylcholine is rather low, although MRs and GRs are fully activated by endogenous corticosterone; this may point to the involvement of additional stress-induced factors modulating the cholinergic responses.     

Sex as Reported in a Recent Sample of Psychological Research

This study is a follow up on the study done by Sara Schwabacher (1972). All the articles in this study were taken from the Journal of Personality and Social Psychology 1974, volume 30, and were reviewed for sex of subjects, type of conclusions drawn, and whether sex was mentioned in the abstract, introduction, or methods section. These results were compared to the Schwabacher study in order to discover if the conditions noted in her study continue to prevail, or whether there has been a change in scientific sampling and reporting procedures.
Contrary to the previous study, the percentage of all male studies show a sharp drop of 15% while all female studies rose 22%. When comparing the amount of single sex studies overgeneralized, all-male studies remained proportionately the same, whereas overgeneralized all-female studies showed an increase of 35.5%. In addition more both-sex articles checked for sex differences than previously reported. The authors discuss the results in relation to the women's movement and scientific decision making. Three suggestions for scientific reporting and procedures are made.     

Language production: Methods and methodologies

Methodological problems have been a longstanding barrier to the systematic exploration of issues in language production. Recently, however, production research has broadened beyond traditional observational approaches to include a diverse set of experimental paradigms. This review surveys the observational and experimental methods that are used to study production, the questions to which the methods have been directed, and the theoretical assumptions that the methods embody. Although tailored to the investigation of language production, most of the methods are closely related to others that are widely employed in cognitive research. The common denominator of these procedures is verbal responding. Because the processing complexities of verbal responses are sometimes overlooked in research on memory, perception, attention, and language comprehension, the methodological assumptions of production research have implications for other experimental procedures that are used to elicit spoken words or sentences.     

A facilitative role for corticosterone in the acquisition of a spatial task under moderate stress

Emotionally charged experiences alter memory storage via the activation of hormonal systems. Previously, we have shown that compared with rats trained for a massed spatial learning task in the water maze in warm water (25°C), animals that were trained in cold water (19°C) performed better and showed higher levels of the stress hormone corticosterone. Here, we examined whether manipulating the levels of corticosterone can determine the strength of spatial information acquisition and retention. Rats were injected with metyrapone (25, 50, and 75 mg/kg, i.p.) or with corticosterone (10 and 25 mg/kg, i.p.) and trained in a massed spatial task in either cold (19°C) or warm (25°C) water. We found that whereas animals injected with vehicle performed well in the spatial task in cold water (moderate stress), rats injected with the intermediate metyrapone dose showed impairment in performance. Moreover, whereas animals injected with vehicle on average did not perform well in warm water (mild stress), rats injected with the lower corticosterone dose showed improvement in performance in warm water. These two mirror experiments of corticosterone blockade and enhancement strongly suggest that corticosterone is instrumental in the acquisition and retention of the spatial learning task.     

Chronic corticosterone-induced deterioration in rat behaviour is not paralleled by changes in hippocampal NF-kappaB-activation

We investigated whether long-lasting stress induced by chronic glucocorticoid (GC) exposure affects activation of brain NF-kappaB and whether these changes are related to functional deterioration and structural changes in the rat hippocampus. Psychometric investigations were conducted using a holeboard test system in 28 one-year-old male Wistar rats. Thereafter, rats were divided into three groups for daily administration of 10 mg corticosterone (treatment) or sesame oil (placebo = sham control for effects of the vehicle) for 60 days. Additional control rats did not receive any treatment or handling until the end of the experiment. Behavioural and cognitive changes were tested again in the holeboard system. Rat body weights and corticosterone concentrations in plasma, hippocampus and urine were determined and adrenal glands were investigated histopathologically. Hippocampal concentrations of corticosterone, NF-kappaB and I-kappaBalpha were determined using RIA, EMSA and Western blotting techniques, respectively. Structural changes in rat hippocampus were measured using magnetic resonance imaging techniques. High peripheral corticosterone concentrations after chronic treatment led to significant reductions in rat body weight. Significant atrophy of both adrenal glands with marked histological deterioration was detected. Furthermore, an increase in hippocampal corticosterone concentrations was observed after chronic administration. Chronic corticosterone treatment also significantly altered behaviour and working and reference memory capacity without changing hippocampal structure. Daily injections of sesame oil in the placebo group, however, were also sufficient to reduce the pellet-finding time. However, neither in the corticosterone group nor in the placebo group were behavioural changes paralleled by significant changes in brain NF-kappaB activation and I-kappaBalpha expression. Thus, cognitive alterations in rats seen after chronic corticosterone exposure are not paralleled by hippocampal NF-kappaB modulation.