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M J Meaney

Publications and source records attributed to M J Meaney.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effects of adrenalectomy and corticosterone replacement on glucocorticoid receptor levels in rat brain tissue: a comparison between western blotting and receptor binding assays.

A sensitive Western blotting technique, using a commercially available antibody, was developed herein to study glucocorticoid receptor (GR) autoregulation in brain tissue. A prominent immunoreactive band at approximately 94 kDa, representing the GR, was observed in soluble fractions prepared from rat hippocampus whereas two bands (approximately 97 and 94 kDa) were detected in frontal cortex preparations. Four-day adrenalectomy significantly increased immunoreactive GR levels in both brain regions. In contrast, adrenalectomized animals implanted with corticosterone pellets of varying concentrations displayed dose-dependent decreases in immunodetectable GR levels. Radioligand binding assays ([3H]dexamethasone +/- RU 28362), performed on these same tissue preparations, revealed a similar pattern of GR response to that measured by Western blotting. However, changes in GR binding capacity were generally greater in magnitude than corresponding changes in immunoreactive GR levels. This discrepancy was most pronounced in adrenalectomized animals administered a bolus of corticosterone 1 h prior to sacrifice where a 60-70% reduction in receptor binding sites occurred, in sharp contrast to the 25-30% decrease in immunoreactive GR levels. Taken together, our findings suggest that Western blotting can be used to study GR regulation in brain tissue and that changes in steroid-binding capacity may not necessarily reflect changes in receptor protein levels.

Adrenalectomy↗
PubMed1995

Sex-specific effects of prenatal stress on hypothalamic-pituitary-adrenal responses to stress and brain glucocorticoid receptor density in adult rats.

Previous research indicates that the offspring of dams exposed to stress during late gestation show altered hypothalamic-pituitary-adrenal (HPA) responses to stress. However, the results are inconsistent and a review of the literature suggests that the effects may differ depending upon the gender of the offspring. In the present study, we measured plasma adrenocorticotropin (ACTH) and corticosterone (B) levels prior to, and at 0, 20, 40 and 70 min following restraint stress in catheterized adult male and female offspring of dams stressed in the last week of gestation (i.e. days 15-19 of gestation). Prenatal stress significantly increased both plasma ACTH and B levels in response to restraint, but only in females; male offspring were largely unaffected. In addition, plasma corticosteroid-binding globulin (CBG) levels were significantly increased in prenatally-stressed females, but not in males. Despite these differences in plasma CBG, estimated free B levels following restraint were also significantly elevated in prenatally-stressed females. We then examined glucocorticoid receptor binding in a variety of forebrain structures. Prenatal stress had no effect on glucocorticoid receptor density in the hypothalamus or hippocampus in either males or females. Differences in glucocorticoid receptor density across groups were observed in the septum, frontal cortex, and amygdala. However, the pattern of observed differences across the groups was not consistent with the pattern of hormonal differences. In summary, the effect of prenatal stress on HPA function is substantially more marked in females than in males. Interestingly, a similar pattern of effects on HPA activity has been reported for prenatal alcohol exposure.

Adrenocorticotropic Hormone↗
PubMed1995

Effects of chronic intermittent cold stress on pituitary adrenocortical and sympathetic adrenomedullary functioning.

Basal and stress-induced pituitary-adrenocortical (PA) and sympathetic adrenomedullary (SAM) function was investigated in rats exposed to chronic intermittent cold stress (4 degrees C for 4 h a day for 21 days; CHR). We found that basal plasma levels of corticosterone (B), corticosteroid-binding-globulin, ACTH, epinephrine (E) and norepinephrine (NE) were similar in CHR and control (CTL) animals. In contrast, activity of the adrenal catecholamine-synthesizing enzyme tyrosine hydroxylase, but not phenylethanolamine-N-methyl transferase, was significantly elevated in CHR compared to CTL. Following exposure to a heterotypic stressor (20 min restraint), plasma levels of B were significantly higher in CHR than CTL, but the stress-induced levels of E and NE were not different between groups. These data suggest that, although basal PA function is not altered by exposure to chronic intermittent cold stress, components of the SAM system are affected by this paradigm, and that co-ordinate facilitation of both PA and SAM responses to a novel stressor is not a necessary consequence of exposure to chronic intermittent stress.

Adrenal Medulla↗
PubMed1995

Glucocorticoids, hippocampal corticosteroid receptor gene expression and antidepressant treatment: relationship with spatial learning in young and aged rats.

The emergence of cognitive deficits in a subgroup of aged rats is associated with increased hypothalamic-pituitary-adrenal axis activity, decreased hippocampal mineralocorticoid and/or glucocorticoid receptor gene expression and neuronal loss. Short-term treatment with antidepressant drugs in young rats increases hippocampal corticosteroid receptor gene expression. In this study, the effects of chronic antidepressant administration on hippocampal mineralocorticoid and glucocorticoid receptor gene expression and spatial memory in young and aged rats were investigated. Young (eight months) and old (22 +/- 1 months) Lister-hooded rats were ranked according to watermaze performance. Matched pairs of rats were treated with amitriptyline (10 mg/kg) or saline daily for nine weeks, then reassessed in the watermaze. Amitriptyline significantly improved spatial memory in the young rats (33% increase in transfer test time) and increased hippocampal mineralocorticoid, but not glucocorticoid receptor messenger RNA expression. By contrast, in aged rats, amitriptyline had no effect on spatial memory or hippocampal corticosteroid receptor gene expression, either in cognitively unimpaired or cognitively-impaired animals. In aged rats, basal plasma corticosterone levels, which were significantly higher than in young animals, correlated negatively with spatial memory, while hippocampal glucocorticoid receptor mRNA expression correlated negatively with plasma corticosterone levels and positively with spatial memory. Amitriptyline had no significant effect on basal morning plasma corticosterone levels in either young or aged rats, but significantly decreased evening corticosterone levels in aged rats. Our data support the notion that corticosterone exerts a concentration-dependent biphasic influence, via selective activation of hippocampal mineralocorticoid and glucocorticoid receptor, on spatial memory. Amitriptyline improves spatial memory in young rats and increases hippocampal mineralocorticoid receptor gene expression. The lack of amitriptyline effect on spatial memory in aged rats may reflect decreased plasticity of both the synaptic processes underlying spatial memory and the regulation of hippocampal mineralocorticoid/glucocorticoid receptor expression, with mineralocorticoid receptors fully occupied due to elevated basal plasma corticosterone levels (in part a consequence of inadequate glucocorticoid receptor function).

Aging↗
PubMed1995

Cholinergic markers in aged cognitively impaired Long-Evans rats.

Aged Long-Evans rats (24-25 months old) were classified into cognitively impaired or unimpaired subgroups based on their performances in the Morris Swim Maze task compared to young controls. Using quantitative in vitro receptor autoradiography, we investigated the status of various cholinergic markers in these two groups and in young adults (six months) animals. The apparent density of [3H]pirenzepine (muscarinic M1) sites was similar in the three groups of rats in various cortical areas, subfields of the hippocampus, medial septum and striatum. Similarly, choline acetyltransferase activity and the density of [3H]hemicholinium-3 (high-affinity choline uptake) and [3H]cytisine (nicotinic) binding sites were also unchanged in the brain regions studied between the aged cognitively impaired, unimpaired and young adult rats. In contrast, significant increases in [3H]AF-DX 384 (muscarinic M2) binding density were observed in various cortical areas and in the molecular layer of the dentate gyrus of aged cognitively impaired versus unimpaired rats and in few cortical regions of old as compared to young animals. Therefore, a selective alteration in the regulation of putative M2 receptor sites is apparent, particularly in the aged cognitively impaired rats. Increases in M2 binding sites could lead to a decrease in the capacity to release acetylcholine, as some of the M2 receptors are believed to act as negative autoreceptors. This could influence cognitive functions as selective M2 blockers have recently been reported to facilitate spatial memory in aged impaired rats [Doods et al. (1993) Life Sci. 52, 497-503: Quirion et al. (1995) J. Neurosci. 15, 1455-1462.

Aging↗
PubMed1995

Hypothalamic-pituitary-adrenal function in chronic intermittently cold-stressed neonatally handled and non handled rats.

Neonatally handled (H) animals, as adults, exhibit lower ACTH and corticosterone (B) responses to a number of acute stressors compared to their non-handled (NH) counterparts. However, little is known about activity within the hypothalamic-pituitary-adrenal (HPA) axis of H and NH animals under conditions of chronic stress. We, therefore, examined HPA function in adult H and NH rats exposed to chronic intermittent cold stress (4 h of 4 degrees C cold a day for 21 days; H CHR and NH CHR) and in control H and NH (H CTL and NH CTL) rats. H CTL and NH CTL animals displayed comparable ACTH and B responses to a single, acute exposure to cold. We found that H CHR animals exhibited lower levels of ACTH, but not B, during the 21st exposure to cold (the homotypic stressor) compared to the first exposure to cold in H CTL; however, ACTH and B levels in NH CHR were not different from those in NH CTL. In contrast, NH CHR animals hypersecreted ACTH and B in response to restraint (the novel, heterotypic stressor) compared to NH CTL and both H groups, whereas H CHR and H CTL animals did not differ in their responses to restraint. These endocrine responses were associated with increased basal median eminence levels of both CRH and AVP in H CHR and NH CHR relative to their control groups (with NH CHR exhibiting the highest absolute levels of each secretagogue), and with decreased glucocorticoid receptor densities in septum of both H CHR and NH CHR. In addition, the expected lower glucocorticoid receptor density in hippocampus and frontal cortex of NH rats compared to H rats was observed. We believe that the difference in glucocorticoid receptor density between H and NH animals in the hippocampus and frontal cortex and the associated differences in secretagogue content in the median eminence are related to the hypersecretion of ACTH and B in the NH CHR relative to the other groups. Furthermore, we hypothesize that an active inhibitory process is involved in the adaptation of HPA responses of H CHR animals to the homotypic stressor, and present a working model of regulation of activity within the CRH/AVP neurons in the PVN.

Adrenocorticotropic Hormone↗
PubMed1995

Stimulation of CRH-mediated ACTH secretion by central administration of neurotensin: evidence for the participation of the paraventricular nucleus.

Central administration of neurotensin (NT) stimulates hypothalamic-pituitary-adrenal (HPA) activity in freely-moving rats. Increases in adrenocorticotropin hormone (ACTH) and corticosterone (B) were observed 15 min following central NT administration and remained elevated for up to 4 h. Of the two NT fragments tested, NT1-8 and NT8-13, only NT8-13 was found to significantly elevate ACTH and B levels. Moreover, NT8-13 activated the HPA axis with a temporal profile similar to NT1-13, suggesting an interaction with the pharmacologically and molecularly characterized NT receptor. Animals pre-treated intravenously with the corticotropin-releasing hormone (CRH) antagonist, alpha-helical CRH, showed attenuated plasma ACTH and B responses to central NT administration. This indicates that CRH receptor activation is necessary for the stimulatory effects of NT on HPA function. Bilateral lesions of the paraventricular nucleus (PVN) of the hypothalamus significantly reduced NT-induced stimulation of ACTH and B release suggesting that the PVN is essential for NT's stimulatory action. Median eminence content studies indicated that acute central NT administration stimulates CRH, but not arginine vassopressin (AVP), release in animals examined 60 min following NT injection. Taken together, these findings suggest that the stimulatory effects of NT on HPA activity occur via specific NT receptors and that one site of action of NT is likely at the level of the PVN where NT elicits the release of CRH.

Adrenocorticotropic Hormone↗
PubMed1995

Neonatal endotoxin exposure alters the development of the hypothalamic-pituitary-adrenal axis: early illness and later responsivity to stress.

The long-term consequences of neonatal endotoxin exposure on hypothalamic-pituitary-adrenal axis (HPA) function were assessed in adult female and male Long-Evans rats. At 3 and 5 d of age, pups were administered endotoxin (Salmonella enteritidis, 0.05 mg/kg, i.p.) at a dose that provokes a rapid and sustained physiological response, but with no mortality. As adults, neonatally endotoxin-treated animals exhibited significantly greater adrenocorticotrophic hormone (ACTH) and corticosterone responses to restraint stress than controls. In addition, dexamethasone pretreatment was less effective in suppressing ACTH responses to restraint stress in endotoxin-treated animals than in controls, suggesting decreased negative-feedback sensitivity to glucocorticoids. Neonatal endotoxin treatment elevated resting-state median eminence levels of corticotropin-releasing hormone (CRH) and arginine vasopressin in adult male animals, and arginine vasopressin in both adult males and females. Neonatal exposure to endotoxin also increased CRH mRNA expression in the paraventricular nucleus of the hypothalamus of adult males, with no difference in females. Finally, glucocorticoid receptor density was reduced across a wide range of brain regions in the neonatal endotoxin-treated, adult animals. These data illustrate the interactive nature of immune and endocrine systems during development. It appears that endotoxin exposure during critical stages of development decreases glucocorticoid negative-feedback inhibition of ACTH secretagogue synthesis, thus increasing HPA responsiveness to stress. The implication of these findings is that exposure to gram-negative LPS in early life can alter the development of neural systems which govern endocrine responses to stress and may thereby predispose individuals to stress-related pathology.

Adrenocorticotropic Hormone↗
PubMed1995

Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats.

Prolonged treatment with stress levels of corticosterone has been reported to produce changes in the hippocampus. In the experiments reported here, we examined for functional and morphological consequences of this treatment. First, young adult or mid-aged male Long-Evans rats were treated for either 1 or 3 months with corticosterone, at a dose sufficient to mimic the elevated hormone levels observed following exposure to mild stress. Two weeks following the termination of treatment, the animals were tested in the Morris water maze to assess spatial learning. No behavioral deficits were observed after 1 month of treatment. A 3 month treatment period also had no effect in young rats, but produced a learning impairment in the mid-aged rats. We then examined whether the effect of elevated corticosterone in mid-aged animals could be produced by a physiological stressor. Mid-aged rats were maintained for 6 months under conditions of low or high social stress. Six months of exposure to high social stress produced significant spatial learning impairments in the Morris water maze. These effects were absent in high social stress animals that had been previously adrenalectomized (with low-level corticosterone replacement), suggesting that elevated glucocorticoid levels mediate the effects of stress on spatial memory in older animals. In a final experiment, mid-aged rats were treated with corticosterone at levels that mimicked those naturally occurring at the diurnal peak (medium-B: 12-17 micrograms/dl) or in response to stress (high-B: 25-32 micrograms/dl). Only rats exposed to high levels of corticosterone demonstrated impaired performance in the Morris water maze.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Facilitation of acetylcholine release and cognitive performance by an M(2)-muscarinic receptor antagonist in aged memory-impaired.

Aged memory-impaired (AI) and unimpaired (AU) 24-25-month-old Long-Evans rats were used to investigate the integrity of various cholinergic markers during normal aging and to establish if alterations can possibly relate to cognitive disabilities. AI and AU rats were classified on the basis of their performance in the Morris swim maze task. Choline acetyltransferase activity (ChAT) was not differentially altered in various cortical and hippocampal areas between these two groups. Similarly, quantitative receptor autoradiography did not reveal significant differences in 3H-pirenzepine/muscarinic M1 and 3H-hemicholinium-3/high-affinity choline uptake binding sites in AI versus AU rats. In contrast, 3H-AF-DX 384/putative muscarinic M2 binding was significantly increased in certain cortical and hippocampal areas of the age-impaired animals. These increments were correlated with decreased in vivo acetylcholine (ACh) release capacity in the AI rats. Most interestingly, the muscarinic M2 antagonist BIBN-99 reversed, in a dose-dependent manner, the impaired ACh release as well as the cognitive deficits observed in the AI group. Similarly, BIBN-99 reversed scopolamine-induced amnesia in young animals. The efficacy of BIBN-99 likely relates to its antagonistic properties on negative muscarinic M2 autoreceptors that are apparently increased in the AI animals, leading to altered ACh release. Taken together, these findings strengthen the role of ACh in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic functions, such as Alzheimer's disease.

Acetylcholine↗
PubMed1995

Increased production of inositol phosphates and diacylglycerol in aged cognitively impaired rats after stimulation of muscarinic, metabotropic-glutamate and endothelin receptors.

Investigations of the functional integrity of receptor-mediated signal transduction are crucial to the understanding of the biochemical cascade underlying memory deficits and neurodegenerative processes of normal and pathological aging. In order to evaluate possible alterations in intracellular transduction components in aging, we studied two groups of 24- to 25-month-old Long-Evans rats selected on the basis of their cognitive performance in the Morris maze task, the aged, cognitively impaired (AI) and cognitively unimpaired (AU) animals. Production of diacylglycerol and inositol phosphates (IPs), two intracellular metabolites generated by the hydrolysis of phosphatidylinositol, were measured in selected brain areas after stimulation by various receptor agonists (1 mM carbachol, muscarinic receptors; 100 microM trans-1-aminocyclopentane-1, 3-dicarboxylate, metabotropic-glutamatergic receptors and 100 nM endothelin-1). Diacylglycerol and IPs were measured following the respective incorporation of [3H]cytidine and [3H]inositol. Data suggest that the stimulation of the inositide cascade via these receptors is at least preserved, or potentiated in the hippocampus and cortex of AI animals. Significant increases in [3H]cytidine and [3H]inositol incorporations were seen in these regions in AI vs. AU and young animals. It remains to be established if these modifications are related directly to the cognitive abilities of the aged rat as AU rats were often comparable to young animals in regard to inositide production. However, higher levels of incorporation in the AI group could reflect modifications in membrane fluidity and possibly increases in IP turnover. Because the IP cascade regulates intracellular Ca++ homeostasis, alterations of this pathway could have complex effects on normal cellular integrity as Ca++ equilibrium must be maintained for adequate neuronal viability and functions.

Aging↗
PubMed1994

Alterations in central catecholamines associated with immune responding in adult and aged mice.

Central catecholamine alterations associated with immune activity are similar to those seen following stressor exposure. Inasmuch as aged animals exhibit more pronounced stressor-provoked alterations of central amines relative to younger animals, it was of interest to determine whether immune challenge would similarly induce more pronounced central amine variations in older animals. Fifteen-month old CD-1 mice challenged with 10(7) sheep red blood cells (SRBC) revealed an equivalent peak splenic plaque-forming cell response (4 days after antigen challenge) to that of 3-month-old mice challenged with 10(6) cells. Neither plasma adrenocorticotropic hormone (ACTH) nor corticosterone levels varied over days following immunization, although ACTH levels were generally higher in the older mice. In both age groups reductions of hypothalamic and locus coeruleus norepinephrine (NE) and increased accumulation of the metabolite MHPG coincided with (or preceded by 24 h) the peak immune response. However, increased accumulation of MHPG in the hypothalamus was greater and occurred earlier in the locus coeruleus of the aged mice. Likewise, at or about the time of peak immune responses nucleus accumbens dopamine (DA) levels were reduced and metabolites elevated in both age groups, while in the prefrontal cortex only DA metabolite levels were elevated. These data are commensurate with previous findings showing that SRBC inoculation may influence central neurotransmitters and that such effects correspond with the time of the peak immune responses. Moreover, in so far as hypothalamic NE utilization is concerned, it seems that the effects of SRBC inoculation are more pronounced in aged animals.

Adrenocorticotropic Hormone↗
PubMed1994

Studies of a neurochemical link between depression, anxiety, and stress from [3H]imipramine and [3H]paroxetine binding on human platelets.

We measured platelet [3H]imipramine and [3H]paroxetine binding in patients with major depression (n = 11), dysthymia (n = 9), generalized anxiety (n = 18) and panic disorder (n = 10), and in healthy controls (n = 13). The [3H]imipramine binding capacity (Bmax) was lower in all patient groups; [3H]paroxetine binding was reduced in anxiety disorders, however, decreases in depression and dysthymia were not significant. There were no differences in the affinity constant (Kd) for either radioligand. We also examined the effects of examination stress on platelet binding in medical students. Compared to after vacation, when binding was similar to controls, [3H]imipramine (n = 19) and [3H]paroxetine (n = 14) Bmax values were significantly decreased during examinations and similar to patient values. Examinations were also associated with an increase in plasma cortisol levels. These findings suggest that there is a neurochemical link between depression, anxiety, and stress, and that disturbances in neurochemical functioning may be associated with specific symptomatology, independent of psychiatric diagnosis.

Adult↗
PubMed1994

Neonatal handling alters serotonin (5-HT) turnover and 5-HT2 receptor binding in selected brain regions: relationship to the handling effect on glucocorticoid receptor expression.

Neonatal handling permanently alters hypothalamic-pituitary-adrenal responses to stress. This effect is, in part, mediated by a handling-induced increase in forebrain glucocorticoid receptor gene expression. The effect of postnatal handling on glucocorticoid receptor expression appears to be mediated by an increase in serotonin (5-HT) activity, acting via a 5-HT2 receptor with a high affinity for 5-HT (i.e. the 5-HT2H receptor). In the present study we examined the nature of the effects of handling on the relevant 5-HT systems. We found that: (1) handling increases 5-HT turnover in regions of the neonatal rat brain where glucocorticoid receptor expression is altered (i.e. the hippocampus and frontal cortex), but not in regions where glucocorticoid receptor expression in unaffected (e.g. hypothalamus and amygdala); (2) handling has no long-term effects on hippocampal or frontal cortex 5-HT turnover, and is actually associated with a decrease in 5-HT concentrations; and (3) handling does not alter 5-HT2 receptor density in the hippocampus or frontal cortex in neonates (although there are surprising effects on 5-HT2 receptor density in the frontal cortex of adult animals). Taken together these data provide further evidence for the importance of 5-HT in mediating the effects of handling on the development of glucocorticoid receptor expression, but suggest that the role of 5-HT is unique to early development; differences in glucocorticoid receptor expression in adult handled and non-handled animals are not associated with long-term differences in either 5-HT levels or 5-HT2 receptors.

Animals↗
PubMed1994

Sex differences in hypothalamic-pituitary-adrenal responding to endotoxin challenge in the neonate: reversal by gonadectomy.

Exposure to endotoxin is known to activate hypothalamic-pituitary-adrenal (HPA) responses in both adult and neonatal animals. We have previously reported that female rat pups exhibit greater HPA responses to endotoxin challenge than males. It is unclear, however, whether observed gender differences at this early age are mediated by gonadal factors. In the present investigation we assessed the effects of neonatal gonadectomy on HPA responses to endotoxin challenge in the developing rat. On the first day of life Long-Evans rat pups were gonadectomized or subjected to sham surgery. On the third day of life the pups were injected i.p. with 0.05 mg/kg Salmonella enteritidis endotoxin. Four hours following injection, trunk blood and tissues were collected for determination of plasma hormones and median eminence corticotropin-releasing hormone (CRH) content. Intact female rat pups were found to exhibit greater plasma adrenocorticotrophic hormone (ACTH) and corticosterone responses to endotoxin challenge compared with male animals. Plasma corticosterone levels, both total and free steroid, were markedly altered by removal of gonads such that responding to endotoxin was elevated in males, while it was reduced in females. In contrast, ACTH responding in male pups was not altered following gonadectomy, whereas female ACTH responses were significantly reduced compared with endotoxin-treated intact controls. CRH levels in the median eminence were reduced following endotoxin challenge to an equivalent extent in both male and female pups and this effect was partially attenuated by the removal of gonadal hormones. These data suggest that sex differences in HPA responses to immune challenge may be mediated at different levels of the HPA axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Aldosterone modulates glucocorticoid receptor binding in hippocampal cell cultures via the mineralocorticoid receptor.

The regulation of corticosteroid receptor expression in the rat brain by adrenal steroids remains controversial. The results of in vivo studies [Brinton and McEwen, 1988; Luttge et al., 1989] suggest that activation of type I receptors can modulate both mineralocorticoid (MR; type I) and glucocorticoid (GR; type II) receptor binding in selected brain regions. The present study utilized primary hippocampal cell cultures from rats sacrificed at E19-20 days of gestation to examine the effects of RU 28362, corticosterone (CORT) and aldosterone (ALDO) on GR binding ([3H]dexamethasone +/- RU 28362). Four days of exposure to 10 nM RU 28362, a highly selective GR agonist, resulted in a robust (approximately 70%) decrease in GR binding. Similar exposure to 10 nM of either CORT or ALDO also produced a significant (50-55%) decrease in GR binding capacity. Scatchard analyses confirmed that the diminished GR binding capacity in response to ALDO was due to a decrease in total number of binding sites (Bmax for Control = 112 +/- 25 fmol/mg vs. ALDO = 48 +/- 12 fmol/mg) with no significant change in the affinity constant. The calculated EC50 from the ALDO concentration response curve was 3.5 nM. Competition studies demonstrated that such low nM concentrations of ALDO were unable to displace specific [3H]dexamethasone +/- RU 28362 binding. Spironolactone, a highly specific MR antagonist, inhibited the ALDO-induced down-regulation of GR binding. These findings support the hypothesis that MR activation can modulate GR binding in hippocampal cells.

Aldosterone↗
PubMed1994

The interaction between prenatal stress and neonatal handling on nociceptive response latencies in male and female rats.

Neonatal handling produces physiological and behavioral changes that persist into adulthood. These effects are opposite to those resulting from prenatal stress (PS). We examined the interaction between PS and handling on nociception in adult male and female rats. Randomly selected pregnant rats were subjected to restraint stress on days 13-17 of gestation for 25 min each day, or left undisturbed. At birth, selected stressed/nonstressed litters were assigned to be handled. handling consisted of 15 min of separation from the dam, once per day, from postnatal days 1-14. At 4 months of age, rats were placed on a 50 degrees C hot plate, and their latencies to paw lick were recorded. Prenatal stress and handling interacted to affect latencies in male rats. Handled (H)/PS rats had significantly lower paw lick latencies than nonhandled (NH)/PS rats (p < 0.05). However, handling had no effect on the male offspring of control dams. Handling elevated paw lick latencies in the female offspring of control dams, an effect that was most pronounced in diestrous vs. estrous rats. The NH/PS rats showed significantly elevated latencies compared to NH/NS rats (p < 0.05). These results suggest that handling effects on nociception are most apparent in rats subjected to PS; in males at least, these effects would otherwise not be present.

Adrenocorticotropic Hormone↗