Stress Hyporesponsive Period Research Articles

Stress in neonatal rats with different maternal care backgrounds: monoaminergic and hormonal responses.

The first 2weeks of life in rats are known as the stress hyporesponsive period because stress responses in pups are diminished as compared to adult animals. However, it is considered a critical period in development in which infant rats are susceptible to environmental events, such as stressful stimuli and quality of maternal care received. These early life events have long-lasting effects, shaping a variety of outcomes, such as stress responsivity. This study investigated the effects of maternal care and sex differences on the response to an aversive stimulus in rat pups from high (HL) and low licking (LL) mothers. Plasma corticosterone, oxytocin (OT), and central monoaminergic activity in 13-day-old rats submitted to cold stress were analyzed. Stress increased plasma corticosterone and marginally decreased hypothalamic dihydroxyphenylacetic acid/dopamine ratio. HL pups showed higher levels of plasma OT than LL pups. The maternal effect was also detected in the hippocampus, in which 5-hydroxyindole-3-acetic acid/serotonin ratio was increased in HL pups, independently of the sex and stress. Investigating the early life events is useful not only into understand the neurobiological and hormonal mechanisms underlying maternal and stressful influences on infant development into a healthy or psychopathological adult phenotype, but also to unveil the immediate outcomes on infancy.

A study on fear memory retrieval and REM sleep in maternal separation and isolation stressed rats

As rapid brain development occurs during the neonatal period, environmental manipulation during this period may have a significant impact on sleep and memory functions. Moreover, rapid eye movement (REM) sleep plays an important role in integrating new information with the previously stored emotional experience. Hence, the impact of early maternal separation and isolation stress (MS) during the stress hyporesponsive period (SHRP) on fear memory retention and sleep in rats were studied. The neonatal rats were subjected to maternal separation and isolation stress during postnatal days 5–7 (6h daily/3d). Polysomnographic recordings and differential fear conditioning was carried out in two different sets of rats aged 2 months. The neuronal replay during REM sleep was analyzed using different parameters. MS rats showed increased time in REM stage and total sleep period also increased. MS rats showed fear generalization with increased fear memory retention than normal control (NC). The detailed analysis of the local field potentials across different time periods of REM sleep showed increased theta oscillations in the hippocampus, amygdala and cortical circuits. Our findings suggest that stress during SHRP has sensitized the hippocampus–amygdala–cortical loops which could be due to increased release of corticosterone that generally occurs during REM sleep. These rats when subjected to fear conditioning exhibit increased fear memory and increased fear generalization. The development of helplessness, anxiety and sleep changes in human patients, thus, could be related to the reduced thermal, tactile and social stimulation during SHRP on brain plasticity and fear memory functions.

Developmental rodent models of fear and anxiety: from neurobiology to pharmacology

Anxiety disorders pose one of the biggest threats to mental health in the world, and they predominantly emerge early in life. However, research of anxiety disorders and fear-related memories during development has been largely neglected, and existing treatments have been developed based on adult models of anxiety. The present review describes animal models of anxiety disorders across development and what is currently known of their pharmacology. To summarize, the underlying mechanisms of intrinsic 'unlearned' fear are poorly understood, especially beyond the period of infancy. Models using 'learned' fear reveal that through development, rats exhibit a stress hyporesponsive period before postnatal day 10, where they paradoxically form odour-shock preferences, and then switch to more adult-like conditioned fear responses. Juvenile rats appear to forget these aversive associations more easily, as is observed with the phenomenon of infantile amnesia. Juvenile rats also undergo more robust extinction, until adolescence where they display increased resistance to extinction. Maturation of brain structures, such as the amygdala, prefrontal cortex and hippocampus, along with the different temporal recruitment and involvement of various neurotransmitter systems (including NMDA, GABA, corticosterone and opioids) are responsible for these developmental changes. Taken together, the studies described in this review highlight that there is a period early in development where rats appear to be more robust in overcoming adverse early life experience. We need to understand the fundamental pharmacological processes underlying anxiety early in life in order to take advantage of this period for the treatment of anxiety disorders.

The behavioral and immunological impact of maternal separation: a matter of timing.

Maternal separation (MS), an early life stressful event, has been demonstrated to trigger neuropsychiatric disorders later in life, in particular depression. Experiments using rodents subjected to MS protocols have been very informative for the establishment of this association. However, the mechanism by which MS leads to neuropsychiatric disorders is far from being understood. This is probably associated with the multifactorial nature of depression but also with the fact that different research MS protocols have been used (that vary on temporal windows and time of exposure to MS). In the present study, MS was induced in rats in two developmental periods: for 6 h per day for 14 days between postnatal days 2–15 (MS2–15) and 7–20 (MS7–20). These two periods were defined to differ essentially on the almost complete (MS2–15) or partial (MS7–20) overlap with the stress hypo-responsive period. Behavioral, immunological, and endocrine parameters, frequently associated with depressive-like behavior, were analyzed in adulthood. Irrespectively from the temporal window, both MS exposure periods led to increased sera corticosterone levels. However, only MS2–15 animals displayed depressive and anxious-like behaviors. Moreover, MS2–15 was also the only group presenting alterations in the immune system, displaying decreased percentage of CD8+ T cells, increased spleen T cell CD4/CD8 ratio, and thymocytes with increased resistance to dexamethasone-induced cell death. A linear regression model performed to predict depressive-like behavior showed that both corticosterone levels and T cell CD4/CD8 ratio explained 37% of the variance observed in depressive-like behavior. Overall, these findings highlight the existence of “critical periods” for early life stressful events to exert programing effects on both central and peripheral systems, which are of relevance for distinct patterns of susceptibility to emotional disorders later in life.

Neuroendocrine responses to social isolation and paternal deprivation at different postnatal ages in mandarin voles

Neonatal isolation and paternal deprivation have long lasting effects on the behavior and neuroendocrine system at adulthood. Whether these effects at adulthood are induced by neonatal changes in relevant neuroendocrine parameters lead by these early-life social experiences is not well understood. Whether monogamous rodents exhibit a stress hypo-responsive period (SHRP) also remains unclear. Using the monogamous mandarin vole, we found that 30 min of isolation did not affect levels of corticosterone (CORT) and adrenocorticotropin (ACTH) at postnatal days 8, 10, and 12 displaying a SHRP, but increased these at postnatal days 4, 14, 16, and 18. Isolation increased vasopressin (AVP)-ir neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) from postnatal days 4 to 12, and up-regulated oxytocin (OT)-ir neurons in the PVN at postnatal days 4 and 8 and SON at postnatal day 4. Paternally deprived pups showed increase in ACTH and CORT after 30 min of social isolation from postnatal days 8 to 14, increase in AVP-ir neurons in the PVN from postnatal days 10 to 14, reduction in OT-ir neurons in the PVN from postnatal days 10 to 14 and in the SON at postnatal days 12 and 14. These results indicate that monogamous mandarin voles display a short SHRP which can be disrupted by paternal deprivation. Central AVP and OT levels may also be altered by paternal deprivation and social isolation. We propose that changes in these neuroendocrine parameters induced by early-life social experiences such as those tested here persist and result.

Social aversive stimuli presented to the mother produce the precocious expression of fear in rat pups

During the stress hypo-responsive period, rat pups do not display fear responses toward adult males, yet they exhibit distress behavior in isolation. Since the mother modulates her offspring's affective development, we hypothesized that by altering the mother's behavior, a prolonged stressful situation would modify the ontogeny of the fear responses and distress behaviors in pups. Therefore, we repeatedly exposed the mother-litter dyad to different socially stressful stimuli and subsequently evaluated in 8-day-old pups their fear responses toward an anesthetized male, as well as their distress behavior in isolation. Our results show that repeated exposure to unfamiliar males and females, which altered maternal behavior by eliciting aggression in the mother, was associated with the precocious fear responses in pups, though without altering their distress behavior in isolation. We propose that the mother, as the principal mediator of environmental influences, provokes the precocious expression of fear in pups through alterations in her maternal behavior.

The behavioral and endocrinological development of stress response in dogs

Endocrinological stress response has been shown to be absent in a specific period of the early life of rodents; this is named the stress-hyporesponsive period (SHRP). The SHRP is a significant period for the appropriate development of infants. In this study, the presence of SHRP in dogs was identified by conducting a 5-min separation test in 142 Labrador retriever puppies in their early socialization period and measuring the changes in urinary cortisol levels. An increase in cortisol after separation was found after 5 weeks of age, suggesting that the SHRP persists until 4 weeks of age in dogs. The distress vocalization during separation changed and the lactating behavior decreased rapidly around 5 weeks of age, suggesting that the endocrinological and emotional aspects of development change at approximately 5 weeks of age and maternal inhibition of cortisol might occur in dogs as well as rodents.

Comparison of Stress-Induced Changes in Adults and Pups: Is Aldosterone the Main Adrenocortical Stress Hormone during the Perinatal Period in Rats?

Positive developmental impact of low stress-induced glucocorticoid levels in early development has been recognized for a long time, while possible involvement of mineralocorticoids in the stress response during the perinatal period has been neglected. The present study aimed at verifying the hypothesis that balance between stress-induced glucocorticoid and mineralocorticoid levels is changing during postnatal development. Hormone responses to two different stressors (insulin-induced hypoglycaemia and immune challenge induced by bacterial lipopolysaccharid) measured in 10-day-old rats were compared to those in adults. In pups corticosterone responses to both stressors were significantly lower than in adults, which corresponded well with the stress hyporesponsive period. Importantly, stress-induced elevations in aldosterone concentration were significantly higher in pups compared both to corticosterone elevations and to those in adulthood with comparable adrenocorticotropin concentrations in the two age groups. Greater importance of mineralocorticoids compared to glucocorticoids in postnatal period is further supported by changes in gene expression and protein levels of gluco- (GR) and mineralocorticoid receptors (MR) and selected enzymes measured by quantitative PCR and immunohystochemistry in the hypothalamus, hippocampus, prefrontal cortex, liver and kidney. Gene expression of 11beta-hydroxysteroid dehydrogenase 2 (11β-HSD2), an enzyme enabling preferential effects of aldosterone on mineralocorticoid receptors, was higher in 10-day-old pups compared to adult animals. On the contrary, the expression and protein levels of GR, MR and 11β-HSD1 were decreased. Presented results clearly show higher stress-induced release of aldosterone in pups compared to adults and strongly suggest greater importance of mineralocorticoids compared to glucocorticoids in stress during the postnatal period.

Maternal deprivation in the middle of a stress hyporesponsive period decreases hippocampal calcineurin expression and causes abnormal social and cognitive behaviours in adult male Wistar rats: Relevance to negative symptoms of schizophrenia

Adverse experiences in early life profoundly influence the developing nervous, endocrine, and immune systems, and also affect human behaviour during adult life and are considered in the pathogenesis of psychiatric disorders. Numerous studies have provided evidence that maternal deprivation in the middle of a stress hyporesponsive period (SHRP) causes multiple behavioural and physiological abnormalities that mimic positive symptoms of schizophrenia in humans. To investigate the neurochemical characteristics of maternal deprivation in the middle of the SHRP in the context of a possible animal model of the symptoms of schizophrenia, we examined calcineurin expression in the hippocampus of maternally deprived rats. To investigate other behavioural characteristics, we behaviourally phenotyped the rats by applying a comprehensive behavioural test battery. The results indicate that maternal deprivation in the middle of the SHRP has no effects on general health, neurological reflexes, sensory function, or motor function, but does have sex-specific effects on a type of anxiety-related behaviour in the open field test and male-specific effects on hippocampal calcineurin expression, social behaviour, and objective memory function. An interpretation of our results and previous studies in the context of the neurodevelopmental hypothesis of schizophrenia suggests that maternal deprivation in the middle of the SHRP in rats models some positive and negative aspects of schizophrenia. The findings regarding the sex-specific effects of maternal deprivation in the middle of the SHRP may become a strong tool for investigating sex differences in the pathogenesis and pathology of schizophrenia in humans.

Effects of lipopolysaccharide exposure at different postnatal time points on the response of LH to homotypic stress in adulthood

Early-life immune stress may have long-lasting effects, known as programming effects, on the physiological response to stress in adulthood. There may be a critical window after birth during which such a challenge can induce long-lasting alterations. However, there are few reports regarding the consequences of this phenomenon for later reproductive function. Here we report on induction by early-life LPS injection of long-lasting alterations in the adult LH response to homotypic immune stress in male rats. First, we investigated developmental changes in the LH response to LPS, since immune challenge during the stress hyporesponsive period can induce long-lasting effects on physiological functions. Rat serum LH concentrations were decreased by LPS (100μg/kg) injection on postnatal day 15 or 25, but not day 10, suggesting that the period prior to postnatal day 10 is the stress hyporesponsive period for LH. Serum LH concentrations and body weight were decreased by adult LPS (400μg/kg) injection in rats given saline or LPS (100μg/kg) on postnatal day 25, but not in rats given LPS (100μg/kg) on postnatal day 10. Expression of hypothalamic IL-1β and TNF-α mRNA, which suppress serum LH during immune stress, were equally increased in these groups by adult LPS (400μg/kg) injection. The present data suggest that the period prior to postnatal day 10 is the critical window in which immune stress can induce long-lasting alterations in the LH response, but that IL-1β and TNF-α are not involved in mediating the altered response.

Neonatal maternal separation in male rats increases intestinal permeability and affects behavior after chronic social stress

Prolonged maternal separation in rats has several effects on health and behavior. Here we investigated how maternal separation might interact with social stress in adulthood on behavior and gastrointenstinal permeability. The effects of either daily 180min long term pup-dam separation (LMS) during the stress hyporesponsive period or daily 10min brief maternal separation (BMS) on behavior, corticosterone and intestinal permeability were investigated, compared to a non-handling (NH) condition in male offspring. The animals from each separation condition were then randomly assigned to adult stress and control conditions, where the stress condition was exposure to 14days of social instability (CSI). Sucrose preference, elevated plus maze behavior and corticosterone were measured. Colitis was experimentally induced by dextran sulfate sodium for 7days, followed by measurement of intestinal permeability using the 51CrEDTA method. Granulocyte marker protein was measured in feces and colons were examined histologically for inflammation. Prior to the social stress, the LMS offspring showed elevated corticosterone levels, lower elevated plus maze activity and less fluid consumption. After social stress, corticosterone levels were suppressed in LMS animals and again they showed less fluid consumption. LMS animals had significantly higher intestinal permeability, but only when also exposed to the social stress in adulthood. The current results support a two-hit model, whereby early life events interact with adult life events in altering animals' vulnerability.

Periodic maternal separation decreases hippocampal neurogenesis without affecting basal corticosterone during the stress hyporesponsive period, but alters HPA axis and coping behavior in adulthood

Although not directly evaluated, the early rise of glucocorticoid (GC) levels, as occur after exposure to adverse early life experience, are assumed to affect hippocampal ontogeny by altering the hippocampus negative feedback on adult HPA axis. To test whether hippocampal ontogeny is affected by early exposure to stress we estimated the survival of recently formed hippocampal granule cells in rat pups subjected to periodic maternal separation (180 min/day; MS180) from postnatal days (PND) 1 to 14. Accordingly, MS180 pups injected with bromodeoxyuridine (BrdU, 50 mg/kg, ip) at PND 5 showed decreased density of doublecortin (DCX) positive BrdU-labeled cells at PND 15. MS180 and AFR pups showed similar corticosterone (CORT) basal levels between PND 3 and 12, whereas adult MS180 rats presented with higher CORT levels than AFR adults. Nonetheless, both AFR and MS180 pups and adults showed similar transient increments of CORT levels in response to stress. In addition, MS180 had no effect on the adult anxiety-like behavior evaluated in the elevated plus maze, but evoked a passive coping strategy in the forced swimming test. The data show that the decrease in hippocampal neurogenesis is an early onset phenomenon, and suggests that adverse experiences alter hippocampal ontogeny without chronic elevation of GC levels.

The effect of different maternal deprivation paradigms on the expression of hippocampal glucocorticoid receptors, calretinin and calbindin-D28k in male and female adolescent rats

Maternal deprivation (MD) is a well-established protocol used to investigate neurobiological changes that are associated with the etiology of and vulnerability to stress-related diseases in animal models. The resulting psychophysiological effects, the timing and duration of these adverse stimuli, and the method by which they exert their effects on the animals remain unclear. This study characterized differences in the hippocampal expression of glucocorticoid receptors (GRs) and the calcium-binding proteins calretinin (CALR) and calbindin-D28k (CALB) in male and female rats that underwent different MD paradigms during the stress hyporesponsive period (SHRP). Both GRs and the two calcium-binding proteins were much more abundant in females than in males. MD paradigms had a significant effect on CALR and CALB expression in both males and females but affected GR levels only in males. Additionally, expression of the two calcium-binding proteins in the hippocampus responded differently to MD-induced stress, especially in females. Taken together, these results indicate that females are able to modulate their response to stress better than males.

Congenital absence of vasopressin and age-dependent changes in ACTH and corticosterone stress responses in rats

The hypothalamic components of the hypothalamo–pituitary–adrenal axis (HPA) are corticotropin-releasing hormone (CRH) and vasopressin. To test the hypothesis that HPA regulation changes with age, we compared ether and bacterial lipopolysaccharide (LPS) injection induced stress reactions in adult and 10-day-old Brattleboro rats, which naturally lack vasopressin owing to mutation of the gene (di/di). The LPS stimulus was used also with V1b receptor antagonist pretreatment (SSR149415). In adult di/di or V1b pretreated rats, we observed normal pituitary and adrenocortical secretory responses, while in all 10-day-old rats stress-induced serum corticosterone increases were marked, but adrenocorticotropin (ACTH) increases were significantly smaller. Compared to control pups the adenohypophysis of the 10-day-old di/di rats responded normally to CRH, but their adrenal glands were hyper-responsive to ACTH, while in adults there was greater secretion at both levels with no difference between the genotypes. The serum transcortin level was higher in adults than pups, with the di/di pups having higher transcortin levels than controls. Hence, using the same stressors in adults and pups with both a genetic model and pharmacological pretreatment, we have shown that the role of vasopressin in ACTH regulation is more important during the neonatal period than in adulthood. Blunted hypophysial sensitivity to CRH and similar adrenal gland sensitivity to ACTH in the pups compared to adults suggest that hypothalamic factors could be responsible for the neonatal stress hyporesponsive period.

Rodent model of infant attachment learning and stress

Here we review the neurobiology of infant odor learning in rats, and discuss the unique role of the stress hormone corticosterone (CORT) in the learning necessary for the developing rat. During the first 9 postnatal (PN) days, infants readily learn odor preferences, while aversion and fear learning are attenuated. Such restricted learning may ensure that pups only approach their mother. This sensitive period of preference learning overlaps with the stress hyporesponsive period (SHRP, PN4-14) when pups have a reduced CORT response to most stressors. Neural underpinnings responsible for sensitive-period learning include increased activity within the olfactory bulb and piriform "olfactory" cortex due to heightened release of norepinephrine from the locus coeruleus. After PN10 and with the decline of the SHRP, stress-induced CORT release permits amygdala activation and facilitates learned odor aversions and fear. Remarkably, odor preference and attenuated fear learning can be reestablished in PN10-15 pups if the mother is present, an effect due to her ability to suppress pups' CORT and amygdala activity. Together, these data indicate that functional changes in infant learning are modified by a unique interaction between the developing CORT system, the amygdala, and maternal presence, providing a learning system that becomes more flexible as pups mature.

Effects on plasma corticosterone levels and brain serotonin from interference with methamphetamine-induced corticosterone release in neonatal rats

Methamphetamine (MA) induces multiple effects in rats including alterations to corticosterone (CORT) and adrenocorticotropic hormone (ACTH). This effect is age dependent showing a U-shaped function similar to that of other stressors during the stress hyporesponsive period. Neonatal MA treatment leads to adult learning and memory impairments, but whether these are related to MA-induced CORT release is unknown. Here in, four methods were tested in neonatal rats previously established in adult rats for inhibiting stress-induced CORT release: inhibiting synthesis (metyrapone (MET) or ketoconazole (KTZ)) or surgically by adrenalectomy or adrenal autotransplantation (ADXA). Pretreatment on postnatal day 11 with MET or KTZ prior to four doses of 10 mg/kg of MA initially suppressed MA-induced increases in plasma CORT, but 24 h later, even with additional inhibitor treatment, a large CORT increase was seen which exceeded that of MA alone. Adrenalectomy blocked MA-induced increases in CORT but caused a secondary effect on brain serotonin (5-HT) and dopamine (DA), causing greater reductions than those caused by MA alone. ADXA inhibited MA-induced CORT release without causing a 24-h CORT increase and did not produce additional effects on brain 5-HT or DA. Neonatal ADXA is a new model for developmental drug or stress experiments designed to test the role of CORT in mediating early effects on later outcomes.

Expression of Glucocorticoid Receptor and Early Growth Response Gene 1 during Postnatal Development of Two Inbred Strains of Mice Exposed to Early Life Stress

Early life stress can elicit profound changes in adult gene expression and behavior. One consequence of early life stress is a decreased expression of glucocorticoid receptors (GRs) in the frontal cortex and hippocampus. However, neither the time of onset nor the mechanism(s) leading to decreased GR expression during postnatal development are known. The present study used two inbred strains of mice that differ in their behavioral responsiveness to stress (Balb/c and C57Bl/6), exposed them to an established paradigm of early life stress (infant maternal separation), and measured their expression of frontal cortical and hippocampal GRs and the putative transcriptional activator of the GR gene, early growth response gene (egr)-1, at defined stages of postnatal development. In both strains, real-time RT-PCR experiments revealed that decreased expression of GR in adolescence and adulthood is, in fact, preceded by increased GR expression during early life stress exposure. Thus, the early life stress-induced disruption of the normal stress-hyporesponsive period during infancy is accompanied by increased GR expression. Moreover, chronic treatment with the antidepressant drug fluoxetine during adolescence or adulthood reversed the effect of early life stress on adult GR mRNA expression. In contrast to the strain-independent effect of early life stress on GR expression, however, changes in egr-1 expression occurred only in Balb/c mice, and unlike the biphasic developmental changes in GR mRNA expression, egr-1 mRNA was decreased throughout postnatal development. Moreover, there was no consistent overlap of anatomic regions affected by decreased GR and egr-1 protein expression. Thus, in Balb/c mice, changes in GR and egr-1 expression can independently contribute to the phenotypes resulting from early life stress exposure. These findings illustrate that the impact of early life stress on gene expression changes is modulated by the genetic background and that the persistent changes in GR and egr-1 expression that arise early during postnatal developmental are reversible by chronic fluoxetine treatment during adolescence and adulthood.

Maternal separation modulates short-term behavioral and physiological indices of the stress response

Early-life stress produces an anxiogenic profile in adulthood, presumably by activating the otherwise quiescent hypothalamic–pituitary–adrenal (HPA) axis during the vulnerable ‘stress hyporesponsive period’. While the long-term effects of such early-life manipulations have been extensively characterized, little is known of the short-term effects. Here, we compared the short-term effects of two durations of maternal separation stress and one unseparated group (US) on behavioral and physiological indices of the stress response in rat pups. Separations included 3 h on each of 12 days, from postnatal day (PND) 2 to 13 (MS2–13) and 3 days of daily, 6-h separation from PND11–13 (MS11–13). On PND14 (Experiment 1), both MS2–13 and MS11–13 produced marked reductions in freezing toward an adult male conspecific along with reduced levels of glucocorticoid type 2 (GR) and CRF type-1 (CRF 1) receptor mRNA in the hippocampus. Group MS2–13 but not MS11–13 produced deficits in stressor-induced corticosterone secretion, accompanied by reductions in body weight. Our results suggest that GR and/or CRF 1 levels, not solely the magnitude of corticosterone secretion, may be involved in the modulation of freezing. In a second experiment, we aimed to extend these findings by testing male and female separated and unseparated pups' unconditioned defensive behaviors to cat odor on PND26, and subsequent cue + context conditioning and extinction throughout postnatal days 27–32. Our results show that maternal separation produced reductions in unconditioned freezing on PND26, with MS2–13 showing stronger deficits than MS11–13. However, separation did not affect any other defensive behaviors. Furthermore, separated rats failed to show conditioned freezing, although they did avoid the no-odor block conditioned cue. There were no sex differences other than weight. We suggest that maternal separation may have produced these changes by disrupting normal development of hippocampal regions involved in olfactory-mediated freezing, not in mechanisms of learning and memory per se. These findings may have direct relevance for understanding the mechanisms by which early-life adverse experiences produce short-term and lasting psychopathologies.

Voluntary exercise reduces the neurotoxic effects of 6-hydroxydopamine in maternally separated rats

Maternal separation has been associated with development of anxiety-like behaviour and learning impairments in adult rats. This has been linked to changes in brain morphology observed after exposure to high levels of circulating glucocorticoids during the stress-hyporesponsive period (P4–P14). In the present study, adult rats that had been subjected to maternal separation (180 min/day for 14 days) during the stress-hyporesponsive period, received unilateral infusions of a small dose of 6-hydroxydopamine (6-OHDA, 5 μg/4 μl saline) into the medial forebrain bundle. The results showed that voluntary exercise had a neuroprotective effect in both non-stressed and maternally separated rats in that there was a decrease in forelimb akinesia (step test) and limb use asymmetry (cylinder test). Maternal separation increased forelimb akinesia and forelimb use asymmetry and reduced the beneficial effect of exercise on forelimb akinesia. It also reduced exploratory behaviour, consistent with anxiety-like behaviour normally associated with maternal separation. Exercise appeared to reduce dopamine neuron destruction in the lesioned substantia nigra when expressed as a percentage of the non-lesioned hemisphere. However, this appeared to be due to a compensatory decrease in completely stained tyrosine hydroxylase-positive neurons in the contralateral, non-lesioned substantia nigra. In agreement with reports that maternal separation increases the 6-OHDA-induced loss of dopamine terminals in the striatum, there was a small increase in dopamine neuron destruction when expressed as a percentage of the non-lesioned hemisphere but there was no difference in dopamine cell number, suggesting that exposure to maternal separation did not exacerbate dopamine cell loss.

Age-related examination of gluco-, and mineralocorticoid effects in vasopressin deficient Brattleboro rats

Event Abstract Back to Event Age-related examination of gluco-, and mineralocorticoid effects in vasopressin deficient Brattleboro rats János Varga1*, Szilamér Ferenczi2, Krisztina Kovács2, Daniela Jezova3 and Dóra Zelena1 1 Institute of Experimental Medicine, Department of Behavioral Neurobiology, Hungary 2 Institute of Experimental Medicine, Laboratory of Molecular Neuroendocrinology, Hungary 3 Slovak Academy of Sciences, Institute of Experimental Endocrinology, Slovakia Previously we proved that vasopressin takes place an age-related manner in the regulation of the hormone levels of the hypothalamo-pituitary-adrenal axis. The effector molecules of the axis are glucocorticoids, which are structurally very similar to mineralocorticoids, and they can act on the same receptors. Therefore the aim of our present work was to examine the age-related influence of vasopressin on gluco- and mineralocorticoid levels and their receptors. Perinatal (10 days old) and adult (10 weeks old) male rats were used. We compared vasopressin deficient Brattleboro rats to their heterozygote littermates. Corticosterone (glucocorticoid) and aldosterone (mineralocorticoid) levels were measured by radioimmunassay under resting conditions and after hypoglycemic stress. Gluco- (GR) and mineralocorticoid receptor (MR) mRNA levels were measrured by quantitative PCR in the hypothalamus and liver. Independetly from the genotype the smaller rats showed only minimal corticosterone increase to stress, while their aldosterone elevation was more expressed compared both to adults and to corticosterone levels. The level of GR and MR mRNA were smaller in the hypothalamus and liver of 10 days old rats. In 10 days old vasopressin deficient rats the corticosterone levels were higher, while their GR and MR mRNA levels were lower in the liver (weeker effect) and higher in the hypothalamus (stronger feedback) compared to heterozygous animals. Our results supports the existence of stress hyporesponsive period, while 10 days old rats showed smaller glucocorticoid elevations with lower receptor levels compared to adult. The opposite (stress hyperresposibility) was true for the pups' aldosterone levels. In general the consequences of vasopressin deficiency was more pronounced in 10 days old animals supporting the view that vasopressin plays a more considerable regulatory role in the perinatal age. Conference: IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010. Presentation Type: Poster Presentation Topic: Homeostatic and neuroendocrine systems Citation: Varga J, Ferenczi S, Kovács K, Jezova D and Zelena D (2010). Age-related examination of gluco-, and mineralocorticoid effects in vasopressin deficient Brattleboro rats. Front. Neurosci. Conference Abstract: IBRO International Workshop 2010. doi: 10.3389/conf.fnins.2010.10.00136 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Apr 2010; Published Online: 28 Apr 2010. * Correspondence: János Varga, Institute of Experimental Medicine, Department of Behavioral Neurobiology, Budapest, Hungary, inajajani@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers János Varga Szilamér Ferenczi Krisztina Kovács Daniela Jezova Dóra Zelena Google János Varga Szilamér Ferenczi Krisztina Kovács Daniela Jezova Dóra Zelena Google Scholar János Varga Szilamér Ferenczi Krisztina Kovács Daniela Jezova Dóra Zelena PubMed János Varga Szilamér Ferenczi Krisztina Kovács Daniela Jezova Dóra Zelena Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.