Blunted neurobiological reactivity and attentional bias to threat underlie stress-related disorders in women survivors of intimate partner violence.

BACKGROUND: Intimate partner violence (IPV) alters women's neurobiological stress response systems. We propose that individual differences early in the attentional processing of threats are associated with these neurobiological mechanisms and contribute to mental illness in this population. METHODS: We assessed attentional bias in relation to threat (AB) in women survivors of IPV (n = 69) and controls (n = 36), and examined overall cortisol secretion using hair cortisol (HC), and stress responsiveness measuring salivary cortisol and α-amylase (sAA) before (T0), and after (T1, T2) an acute psychosocial stress task (Trier Social Stress Test). We used repeated-measures ANCOVAs to explore the associations between Group (IPV, control) and AB with acute stress response, and regression models to examine the associations with mental health symptoms. RESULTS: There were no between-group differences in HC levels. An interaction between Group and AB was found regarding cortisol reactivity (p < 0.05). IPV women with threat avoidance AB showed a blunted cortisol response compared to controls and to IPV participants with threat vigilance AB. The association between sAA reactivity and the interaction between Group, AB, and time approached significance (p = 0.07), with a trend to lower sAA levels particularly in IPV women with threat avoidance AB. Group and cortisol reactivity were associated with symptoms of depression, generalized anxiety, and post-traumatic stress disorder (8-20% explained variance). CONCLUSIONS: Threat avoidance AB is associated with blunted acute cortisol response among women exposed to chronic stress (IPV). Experiencing IPV and acute cortisol response appear to be clearly implicated in long-term mental health problems.

Design and optimization of a single-use optical sensor based on a polymer inclusion membrane for zinc determination in drinks, food supplement and foot health care products.

A single-use optical sensor was designed for Zn(II) determination based on the immobilisation of the colorimetric reagent 2-acetylpyridine benzoylhydrazone (2-APBH) in a polymer inclusion membrane (PIM) adhered on the surface of an inert rectangular strip of polyester (Mylar). Different components for the membrane preparation were tested and those resulting in membrane with good appearance, proper physical and optical properties and ease of preparation were selected. Factorial design 23 with three replicates of the central point was applied for the optimisation of the membrane composition. The optimal composition consisted of 2.5 g of poly(vinyl chloride) (PVC), 4 mL of tributyl phosphate (TBP) and 0.04 g of 2-APBH. The optode showed a linear dynamic range from 0.03 (detection limit) to 1 mg L-1 of Zn(II) ions with a response time of 30 min in aqueous solution at pH 6 and a relative standard deviation of 3.90% for 0.4 mg L-1 of Zn(II). The sensor exhibited good selectivity to Zn(II) over other commonly ions. It was successfully applied to the determination of Zn(II) in a water certified reference material, spiked tap water, vitamin-mineral drink, food supplement and foot health care products, as contribution to the concern about this heavy metal due to its significant role in many biological and physiological processes although toxicant at high doses.

Marked dissociation between hypothalamic-pituitary-adrenal activation and long-term behavioral effects in rats exposed to immobilization or cat odor.

Exposure of rodents to cats or certain cat odors results in long-term behavioral effects reminiscent of enhanced anxiety that have been considered to model post-traumatic stress disorder. However, other severe stressors such as tail-shock or immobilization in wooden boards (IMO) appear to induce shorter lasting changes in anxiety. In addition, there are controversial results regarding the effects of urine/feces odors. In the present work, we studied in two experiments the relationship between the degree of stress experienced by the animals during exposure to IMO, urine odors or fur odors (as assessed by hypothalamic-pituitary-adrenal activation and plasma glucose) and the short- and long-term behavioral consequences. In the first experiment, rats were individually exposed for 15 min to a novel environment (white large cages) containing either clean cat litter (controls) or litter soiled by cats (urine odors). Half of the rats in each condition were left to freely explore the environment whereas the others were subjected to immobilization (IMO) within the cages. Although ACTH, corticosterone and glucose responses to IMO were much stronger than those to the white cages with clean litter or urine odors (which did not differ from each other), no effect of treatments on anxiety-like behavior in the elevated plus-maze (EPM) were found one week later. However, previous IMO exposure did cause sensitization of the ACTH response to the EPM. In the second experiment, the response to white large cages containing either no odor (controls), litter soiled by cats (urine odor) or a cloth impregnated with cat odor (fur odor) was compared. Urine and fur odors elicited similar ACTH and corticosterone responses that were higher than those of controls, but plasma glucose levels were slightly higher in rats exposed to fur odor. When compared to controls, activity was only diminished in the novel cages containing fur odor. Similarly, fur odor-exposed rats, but not those exposed to urine odor, showed signs of enhanced anxiety in the EPM seven days later, although the ACTH response to the EPM was similar in the three groups. The present data demonstrate: (a) a marked dissociation between the degree of ACTH, corticosterone and glucose responses to stressors and their long-term anxiety-like effects; (b) that the type of cat odor is critical in determining the short-term and long-term physiological and behavioral consequences of exposure; and (c) that plasma ACTH released during brief exposure to the EPM does not appear to reflect anxiety-like behavior.

Previous exposure to immobilisation and repeated exposure to a novel environment demonstrate a marked dissociation between behavioral and pituitary-adrenal responses.

Activation of the hypothalamus-pituitary-adrenal (HPA) axis is presumably related to the degree of novelty and considered to reflect emotional reactivity. Exposure to novel environments can allow us to simultaneously evaluate both behavior and HPA activation and therefore it is an appropriate design to directly study the relationship between both responses. In the present experiment, we studied how previous exposure to a severe stressor (2 h of immobilisation, IMO, 5 days before testing) and repeated exposure to the same novel environment (a holeboard, HB) altered behavioral and HPA response to the HB. Previous exposure to IMO did not alter any behavior during the first exposure to the HB (5 min), but elicited a greater ACTH response as compared to stress-naive rats. However, corticosterone response did not differ between groups, probably because maximum corticosterone levels are never reached before 15-20 min. Repeated exposure of IMO and stress-naive rats to the HB every other day resulted in progressively lower levels of activity/exploration in both groups, whereas the ACTH and corticosterone responses were basically maintained intact over the days. The present results demonstrate a double dissociation between behavior and HPA activation in the HB. First, a single exposure to IMO elicited a long-lasting sensitisation of the HPA axis that apparently was not a direct consequence of fear/anxiety elicited by the novel environment. Second, progressive familiarisation of the animals with a novel environment resulting in apparently lower levels of motivation to explore did not appear to reduce the stressful properties of the situation as evaluated by ACTH release.

Litter size affects emotionality in adult male rats.

The role of natural variations in pre-weaning litter size in rodent adult emotionality and the importance of maternal care as a possible mediating factor have been frequently neglected. To address these issues, maternal behaviour of Sprague-Dawley dams differing in natural number of pups was studied for the first seven postnatal days. Later, adult behaviour of representative male offspring was studied in the elevated plus-maze, the circular corridor, the dark-light box and the forced swimming test. Three groups of offspring were selected in function of the number of littermates: L<10 group (less than 10 pups per dam), L10-15 (between 10 and 15 pups per dam) and L>15 group (more than 15 pups per dam). L<10 litters showed a reduced habituation of activity across time in a circular corridor and as compared to L>15 litters, L<10 litters showed a lower activity during the first 5 min of exposure to the circular corridor. L<10 litters had also higher signs of anxiety in the elevated plus-maze, in comparison to the other two groups. In addition, L<10 litters showed in the forced swimming test reduced struggling and more mild swimming behavior than the other two groups. These abnormalities in L<10 litters are not explained by maternal behavior since they received individually more maternal care than L>15, as assessed by total licking-grooming observed during the whole observation period divided by number of pups. Although previous data from several laboratories have demonstrated that low maternal care is associated with heightened emotionality at adulthood, the present results suggest an important contribution of spontaneous litter size to adult emotional behavior that cannot be explained by concomitant changes in maternal care.

An approach to an acute emotional stress reference scale. / Aproximacion a una escala de referencia de estres emocional agudo.

INTRODUCTION: The clinical diagnosis aims to identify the degree of affectation of the psycho-physical state of the patient as a guide to therapeutic intervention. In stress, the lack of a measurement tool based on a reference makes it difficult to quantitatively assess this degree of affectation. AIM: To define and perform a primary assessment of a standard reference in order to measure acute emotional stress from the markers identified as indicators of the degree. SUBJECTS AND METHODS: Psychometric tests and biochemical variables are, in general, the most accepted stress measurements by the scientific community. Each one of them probably responds to different and complementary processes related to the reaction to a stress stimulus. The reference that is proposed is a weighted mean of these indicators by assigning them relative weights in accordance with a principal components analysis. RESULTS: An experimental study was conducted on 40 healthy young people subjected to the psychosocial stress stimulus of the Trier Social Stress Test in order to perform a primary assessment and consistency check of the proposed reference. The proposed scale clearly differentiates between the induced relax and stress states. CONCLUSIONS: Accepting the subjectivity of the definition and the lack of a subsequent validation with new experimental data, the proposed standard differentiates between a relax state and an emotional stress state triggered by a moderate stress stimulus, as it is the Trier Social Stress Test. The scale is robust. Although the variations in the percentage composition slightly affect the score, but they do not affect the valid differentiation between states.

TITLE: Aproximacion a una escala de referencia de estres emocional agudo.Introduccion. El diagnostico clinico persigue identificar el grado de afectacion del estado psicofisico del paciente como orientacion hacia la intervencion terapeutica. En el estres, la falta de un instrumento de medicion por comparacion con una referencia dificulta la valoracion cuantitativa del nivel de afectacion. Objetivo. Definir y hacer una primera validacion de un patron de referencia para la medida del estres emocional agudo a partir de marcadores identificados como indicadores del nivel. Sujetos y metodos. En general, las medidas mas solidas y aceptadas de estres por la comunidad cientifica son los test psicometricos y las variables bioquimicas. Cada uno de ellos responde probablemente a procesos distintos y complementarios de la reaccion frente a un estimulo estresante. La referencia que se propone es una media ponderada de estos indicadores, asignandoles pesos relativos de acuerdo con un analisis de componentes principales. Resultados. Para una primera aproximacion y verificacion de coherencia de la referencia propuesta, se ha utilizado un estudio experimental con una muestra de 40 jovenes sanos sometidos al estimulo estresante psicosocial del Trier Social Stress Test. La escala propuesta diferencia netamente entre los dos estados con distintos niveles de estres inducido. Conclusiones. Aceptando la subjetividad de la definicion, y a falta de una validacion posterior con nuevos datos experimentales, el patron propuesto diferencia entre un estado de relax y uno de estres emocional generados con un estimulo estresante moderado, como es el Trier Social Stress Test. La escala es robusta, ya que variaciones en la composicion porcentual repercuten ligeramente en la puntuacion, pero no en la diferenciacion valida entre estados.

IL-6 and TNF-α in unmedicated adults with ADHD: Relationship to cortisol awakening response.

There is preliminary evidence that the immune system's cytokines may have impact on ADHD in children. Nevertheless, studies exploring the possible role of pro-inflammatory cytokines in adults with ADHD are lacking. This study aimed to assess differences in serum IL-6 and TNF-α between patients and controls and their possible relationship to resting cortisol. 108 adults with ADHD (DSM-IV), 44 inattentive and 64 combined, age ranging between 18 and 55 years, and 27 healthy controls were included. Major psychiatric disorders and organic comorbidities were excluded. Serum samples for IL-6 and TNF-α and salivary samples to assess cortisol awakening response were collected on the same day. Analysis of variance was applied to study differences in IL-6 and TNF-α between groups. Pearson correlations were used to study associations between IL-6, TNF-α, and CAR. There were no significant differences in serum IL-6 or TNF-α levels between patients and controls or between combined and inattentive patients. Negative associations between IL-6 (r=-0.386, p=0.020), TNF-α (r=-0.372, p=0.023) and cortisol awakening response were found in the inattentive subtype, whereas no association was seen in the combined subtype. A negative correlation between IL-6 and cortisol was also present in the control group (r=-0.44, 0.030). The peripheral pro-inflammatory markers, IL-6 and TNF-α, do not appear to be primarily involved in ADHD in adults, although the role of other inflammatory markers cannot be ruled out. The differences regarding the association between IL-6 and TNF-α and morning cortisol response suggest possible underlying neurobiological differences between the inattentive or combined patients that merit further studies.

Social stress is as effective as physical stress in reinstating morphine-induced place preference in mice.

RATIONALE: Relapse to drug-seeking in abstinent heroin addicts and reinstatement in experimental animals are observed when exposed to drug-associated stimuli or cues, the drug itself, and stressful events. It has been shown that footshock-induced stress increases the rewarding effects of opiates, delays extinction, and induces the reinstatement of drug-seeking. However, the effects of social stress on the reinstatement of opiate-seeking after extinction has not been studied. OBJECTIVES: The role of physical (restraint and tail pinch) and social (social defeat) stressors on the reinstatement of morphine-induced conditioned place preference (CPP) was evaluated. METHODS: Adult male OF1 mice were conditioned with 10, 20, or 40 mg/kg of morphine or saline. Only morphine-conditioned animals acquired CPP. All mice underwent extinction sessions until the CPP was extinguished. Then, the effects of physical or social stress on the reinstatement of CPP were evaluated. Morphine- and saline-conditioned animals were exposed to the respective stressor or control stress condition immediately or 15 min before reinstatement tests. In experiment 1, animals underwent restraint for 15 min. In experiment 2, animals were exposed to tail pinch or placed in a cage without any manipulation for 15 min. In experiment 3, animals performed an agonistic encounter with an isolated or anosmic mouse or were placed in a cage without any social contact or manipulation. RESULTS: Restraint, tail pinch, and social defeat in an agonistic encounter with an isolated mouse produce the reinstatement of CPP in morphine-conditioned animals. CONCLUSIONS: These data demonstrate that social stress is as effective as physical stress in reinstating morphine-seeking.

Influence of reactivity to novelty and anxiety on hypothalamic-pituitary-adrenal and prolactin responses to two different novel environments in adult male rats.

Since stressor-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis is involved in some stress-related pathologies, much attention has been paid in laboratory animals to the study of the relationship between endocrine, particularly HPA, responsiveness to stressors and other individual characteristics, such as reactivity to novelty and fear/anxiety. In the present study, adult male rats were classified as high or low reactive to novelty (HR versus LR), as a function of the horizontal activity displayed during 30 min in a circular corridor, and as high or low anxiety (HA versus LA) as a function of the time spent in the open arms of the elevated plus-maze. Then, the behavioural and hormonal response to two distinct novel environments (the hole-board and the light-dark) was assessed in the same subjects, using a counterbalanced design. Plasma prolactin, ACTH and corticosterone responses to the hole-board were higher than to the light-dark, a good correlation between the two tests being found for each hormone. Whereas the hormonal response to the novel environments was not affected by anxiety, HR rats showed a consistently higher HPA response than LR rats when the criteria to classify the animals were the activity during the first 15 min in the circular corridor, but not when the activity during the second 15 min was considered. Neither trait affected prolactin response. The present results demonstrate a good within-individual consistency of the endocrine response to novel environments and support the hypothesis of a higher HPA response to stressors for HR versus LR rats. In contrast, no contribution of fear/anxiety to endocrine responsiveness was observed.

A single dose of metyrapone caused long-term dysregulation of the hypothalamic-pituitary-adrenal axis in the rat.

There is evidence that metyrapone (MET), apart from its inhibition of 11-beta steroid hydroxylation, may exert some stress-like effects in the brain, including the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the induction of c-fos. Since a single exposure to some stressors has been found to exert long-term effects on the HPA axis, we hypothesized that a single dose of MET (200 mg/kg, s.c.) could exert even stronger effects, due to the combination of its stressful properties with the lack of constrain of the HPA axis by glucocorticoids. Whereas the inhibitory effect of the drug on corticosterone secretion lasted less than 24 h, its stimulatory effect on the HPA axis could be seen for at least 2 days after the injection. Surprisingly, on day 8, an exacerbated HPA response to immobilization stress was observed in MET rats, despite complete normalization of resting levels of HPA hormones. At this time it was also observed, under basal conditions, increased levels of mRNA for CRH and arginin-vasopressin in the parvocellular region of the paraventricular nucleus of the hypothalamus (pPVN), along with reduced mRNA for glucocorticoid receptors in dentate gyrus and hippocampus CA1, but not in pPVN or medial prefrontal cortex. These data suggest that a single MET administration can exert a marked and long-lasting dysregulation of both resting and stress-induced activity of the HPA axis. Thus, attention should be paid to these properties when using the drug to study the functional role of glucocorticoids.

Perseverance of exploration in novel environments predicts morphine place conditioning in rats.

Reactivity to novelty has been related to operant drug self-administration but does not seem involved in the conditioned place preference (CPP). To further assess this issue our aims were to investigate: (1) the importance of the initial versus delayed activity in the novel environment to predict the CPP induced by morphine; (2) the separate contribution of trait anxiety in morphine CPP. Male Sprague-Dawley rats were exposed to a circular corridor for 30 min to assess reactivity to novelty and to the elevated plus-maze and the light-dark tests as measures of anxiety and morphine CPP was then studied (three pairings with 5 mg/kg s.c. morphine and three with saline). Delayed activity in the corridor (16-30 min) correlated positively with CPP score, whereas the initial activity (0-15 min) did not. High-responders (HR), those more active during the second half of the corridor, developed morphine CPP in contrast to low-responders (LR). Also, HR and LR did not differ in anxiety nor any plus-maze or light-dark test measure correlated with CPP behaviour. Enhanced vulnerability to develop morphine CPP is predicted by a higher delayed activity in a novel environment, regardless of anxiety.

Response of anterior pituitary hormones to chronic stress. The specificity of adaptation.

The effect of chronic noise stress on the response of anterior pituitary hormones to the same or to another stressor (forced swimming) was studied in adult male Wistar rats. Both acute stressors increased corticosterone, prolactin, LH and TSH secretion and inhibited GH secretion. Previous chronic exposure to noise reduced corticosterone response to the same stimulus without modifying corticosterone response to a novel acute stress. Neither prolactin nor TSH responses to acute noise were reduced by previous chronic exposure to noise. Since chronic noise increased basal levels of LH and decreased those of GH, the response of these hormones to acute stress was expressed as percent changes of their respective basal values. It was found that chronically stressed rats showed diminished LH response to noise but not to forced swimming. GH showed the same pattern without reaching statistical significance. These data indicate that the response of some anterior pituitary hormones can adapt after repeated exposure to the same stressor. When adaptation occurred, this was specific for the stressor which the animals were repeatedly exposed to. The pituitary-adrenal axis appears to be the most reliable index of adaptation to chronic stress among all the anterior pituitary endocrine axes.

IL-6 deficiency leads to increased emotionality in mice: evidence in transgenic mice carrying a null mutation for IL-6.

The role of interleukin-6 (IL-6) on emotional behavior was studied in two experiments using transgenic mice carrying a null mutation for IL-6 (IL-6(-/-)). In the first experiment, IL-6(-/-) mice were compared with the two wild-type strains contributing to the genetic background of the transgenic mice, namely C57BL/6J and 129/SvJ, as well as with the F2 offspring of C57BL/6J x 129/SvJ mice. The two parental strains differed substantially in terms of emotional reactivity, suggesting that the F2 offspring were more appropriated for analyzing the effect of the null mutation. IL-6(-/-) mice showed lower levels of ambulation in the holeboard, and lower levels of exploration of the open arms of the plus-maze, than the wild-type F2 C57BL/6J x 129/SvJ mice. In the second experiment, IL-6(-/-) mice were backcrossed for 10 generations to C57BL/6J mice to decrease the uncertainty of the effect of the genetic background, and when compared with wild-type C57BL/6J mice in the holeboard and the plus-maze, the same results were obtained. Therefore, IL-6(-/-) mice seem to be more emotional than their appropriate controls, suggesting that the major cytokine IL-6 is involved in the control of emotionality.

The hypothalamic-pituitary-adrenal and glucose responses to daily repeated immobilisation stress in rats: individual differences.

It is accepted that there are important individual differences in the vulnerability to stress-induced pathologies, most of them associated to the hypothalamic-pituitary and sympatho-medullo-adrenal axes, the two prototypical stress-responsive systems. However, there are few studies specifically aimed at characterising individual differences in the physiological response to daily repeated stress in rats. In the present work, male rats were submitted to repeated immobilisation (IMO) stress (1 h daily for 13 days) and several samples were taken at specific days and time points. Animals only subjected to blood sampling procedure served as controls. Daily adrenocorticotropic-hormone (ACTH), corticosterone and glucose responses to immobilisation (that included the post-immobilisation period) progressively declined over the days. In addition, repeated immobilisation resulted in decreased relative thymus weight, increased relative adrenal weight, elevated corticotropin-releasing factor (CRF) mRNA levels in the hypothalamic paraventricular nucleus (PVN), and down-regulation of glucocorticoid receptor gene transcription in hippocampus CA1. However, only CRF mRNA levels in the paraventricular nucleus correlated with the ACTH (on day 1) and corticosterone responses (from day 4-13) to immobilisation. When the animals were classified in three groups on the basis of their plasma ACTH levels immediately after the first immobilisation, individual differences in the ACTH response progressively disappeared on successive exposures to the stressor, whereas those in corticosterone and glucose were more sustained. The present results suggest that there are individual differences in the physiological response to stress that tend to be reduced rather than accentuated by repeated exposure to the stressor. Nevertheless, this buffering effect of repeated stress was dependent on the particular variable studied.

A single lipopolysaccharide administration is sufficient to induce a long-term desensitization of the hypothalamic-pituitary-adrenal axis.

We have previously shown that a single exposure of adult rats to a severe emotional stressor such as immobilization is able to exert a long-term desensitization of the response of the hypothalamic-pituitary-adrenal (HPA) axis to the same stimulus when applied days to weeks later. Surprisingly, the intensity of the effect increased with time elapsed between the two exposures, suggesting that we are dealing with a new type of stress-associated phenomenon. Taking into account the clinical importance of tolerance to endotoxin, in the present study we assessed whether a single exposure to an immunological stressor such as lipopolysaccharide can induce effects similar to those of immobilization. Rats injected with lipopolysaccharide (1 mg/kg) showed a reduction of the response of the corticotropin-releasing factor mRNA in the paraventricular nucleus of the hypothalamus after a new lipopolysaccharide injection 4, but not 2 weeks later. In an additional experiment using a different blood sampling procedure, adrenocorticotropin hormone, corticosterone and tumor necrosis factor-alpha responses were reduced approximately to the same extent by previous experience with lipopolysaccharide either 1 or 4 weeks before. Our data suggest that a previous single exposure to lipopolysaccharide induces a long-lasting tolerance of the HPA axis that likely involves some kind of learning-like brain plasticity.

Differences in prolactin and LH responses to acute stress between peripuberal and adult male rats.

Pituitary-adrenal, pituitary-gonadal and prolactin responses to acute stress (restraint) were studied in peripuberal and adult male rats. The pituitary-adrenal response to restraint stress did not differ in peripuberal and adult rats. Prolactin increase during stress was less marked in peripuberal animals. While an increase in LH during stress was observed in adult rats, peripuberal animals did not respond to stress. Testosterone levels were also lower in peripuberal than in adult rats. Diminished LH and prolactin responses to stress in peripuberal rats did not appear to be due either to increased pituitary-adrenal activity or to altered pituitary responsiveness to LHRH and dopamine respectively. Peripuberal rats were also more sensitive to the action of morphine on LH and prolactin release than were adult rats, suggesting that endogenous opioids may be involved in the LH and prolactin responses to acute stress. Differences in the maturation of central mechanisms rather than in pituitary response appear to be responsible for the differing responses to acute stress.

Acute stress attenuates but does not abolish circadian rhythmicity of serum thyrotrophin and growth hormone in the rat.

The effects of acute immobilization (IMO) on daily rhythms of corticosterone, thyroid-stimulating hormone (TSH) and growth hormone (GH) were studied in adult male rats. Two hours of IMO increased serum corticosterone, this increase still being observed 3 h after finishing stress exposure. In the dark period corticosterone levels did not differ in control and IMO rats, but higher levels were observed again in the morning of the day after. Immobilization lowered serum GH and TSH levels throughout the 24-h period that followed exposure to the stressor. Such an effect was more marked in GH than in TSH. In addition, GH, but not TSH, levels were found to be reduced significantly by IMO at 08.30 h of the next day. None the less, daily rhythms of GH and TSH were still persistent and roughly similar to those of control rats. The daily rhythm of food intake was measured in a separate experiment and it was observed, as expected, that IMO reduced food intake only in the dark period of the lighting cycle. It appears therefore unlikely that IMO-induced anorexia was the major factor responsible for the inhibition of GH and TSH caused by IMO at 11.00 and 19.00 h, considering that the amount of food intake was very low and similar in control and IMO rats during this period. However, anorexia might have contributed to inhibition of GH and TSH secretion afterwards. Thus, in a third experiment we studied the contribution of IMO-induced anorexia to the changes in hormone levels observed 24 h after stress by introducing a group of pair-fed rats. It was found that IMO, but not pair-feeding, reduced TSH levels, whereas a similar reduction of GH was found in the two conditions. It might be concluded that acute stress transiently altered corticosterone secretion, the only long-lasting effect being a slight increase in its morning levels on the following stress. Immobilization also causes an inhibition of GH and TSH secretion in the rat that persists for several hours after finalization of exposure to the stressor, but daily rhythms were still apparent. It appears that the contribution of stress-induced anorexia is different in GH than in TSH. In conclusion, an acute severe stressor such as IMO, although modifying circulating levels of some hormones, particularly in the hours following exposure to the stressor, did not appear to interfere greatly with the expression of circadian rhythms of anterior pituitary hormones.

Abnormalities of hypothalamic-pituitary-adrenal and hypothalamic-somatotrophic axes in Fawn-Hooded rats.

Fawn-Hooded (FH) rats show central and peripheral abnormalities in serotoninergic functions and have attracted attention as an animal model of some pathologies, including depression and hypertension. In addition, these rats show a reduced growth rate. As the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in both depression and hypertension, and the hypothalamic-somatotrophic (HSM) axis has a major role in growth, these two endocrine axes were characterised in FH rats as compared with outbred Sprague-Dawley (SD) rats in basal conditions. FH rats showed normal serum ACTH and corticosterone concentrations, but reduced serum corticosterone binding capacity. At a central level, normal expression of mRNA for glucocorticoid type II receptors in the hippocampal formation and mRNA for corticotrophin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus were observed in FH rats, whereas expression of mRNA for CRF in the central nucleus of the amygdala was enhanced compared with the expression in SD rats. Serum GH concentrations were normal in FH rats, IGF-I tended to be lower, and mRNA for somatostatin (SRIF) in the periventricular nucleus of the hypothalamus was significantly lower in FH rats than in SD rats. The reduced SRIF gene expression in rats with normal or slightly reduced GH and IGF-I, respectively, might be secondary to a defective central and peripheral response to IGF-I, compatible with the reduced growth of FH rats. The present results suggest that FH rats have abnormalities in both HPA and HSM axes that might be related to some of their physiopathological characteristics.

Chronic stress alters pituitary-adrenal function in prepubertal male rats.

The effect of exposure to chronic stress on the pituitary-adrenal axis was studied in prepubertal rats. The chronic stress consisted of exposing the animals 6 days a week for 32 days to one stressor randomly chosen among several each day. Chronic stress did not alter either food intake or body weight gain. However, it was stressful for the rats, as they had increased adrenal weights. Chronically stressed rats showed normal pituitary-adrenal basal activity and normal ACTH responses to a novel, acutely applied stressor. However, this treatment resulted in higher corticosterone response to an acute stressor, as a consequence of enhanced adrenocortical response to ACTH. In addition, chronic stress induced increasing sensitivity of the adrenal to the inhibitory action of dexamethasone. Exploratory activity and defecation rate in a novel environment were not affected by the chronic stress. All these data indicate that behavioral and endocrine changes induced by chronic stress were somewhat different from those previously found in adult rats. Prepubertal rats appear to be less sensitive than adult rats to the chronic stress we used.

Individual differences in the recovery of the hypothalamic-pituitary-adrenal axis after termination of exposure to a severe stressor in outbred male Sprague-Dawley rats.

Individual differences in the speed of recovery of the hypothalamic-pituitary-adrenal (HPA) axis response to immobilization in wooden boards (IMO) were studied in two experiments using a normal population of two months old male outbred Sprague-Dawley rats. In a first experiment, rats were subjected to 2 h IMO and were sampled, together with a group of control rats, at various times by the tail-nick procedure. Rats were divided into three groups depending on plasma corticosterone levels observed 2 h after termination of exposure to IMO: fast recovery (FR), intermediate recovery (IR) and slow recovery (SR). When the samples obtained at different times were classified in function of the three groups obtained at 2 h post-stress, no differences among groups were observed just after IMO. However, in the morning on the day after stress, all IMO rats showed higher plasma corticosterone levels than controls, but SR rats showed higher levels than FR rats, whereas IR rats were in between. Neither ambulatory activity in the open-field nor behaviour in the plus-maze was related to the HPA responsiveness to IMO. In a second experiment, there were no between-groups differences in ACTH and corticosterone levels obtained just after IMO. However, at 2 h, post-stress ACTH levels followed the same pattern as corticosterone. These data indicate that individual differences in the speed of recovery of the HPA axis after exposure to a severe stressor are not related either to individual differences in fear/anxiety or to the HPA response during exposure to the stressor. These individual differences in the capability to terminate the activation of the HPA axis after stress might be related to individual differences in the predisposition to develop stress-induced pathology.