Search PubMed⌕ Search

Biomedical subjects

M J Meaney

Publications and source records attributed to M J Meaney.

At least 109 records · Page 6Linked to original sources
PubMed1992

Serotonergic regulation of type II corticosteroid receptor binding in hippocampal cell cultures: evidence for the importance of serotonin-induced changes in cAMP levels.

The development of the hypothalamic-pituitary-adrenal response to stress is profoundly altered by environmental events. One target for environmental regulation within the hypothalamic-pituitary-adrenal axis is the hippocampal type II corticosteroid (or glucocorticoid) receptor system, which mediates the negative-feedback effects of glucocorticoids on hypothalamic-pituitary-adrenal activity. Thus, adult rats handled early in life show increased hippocampal type II corticosteroid receptor density and increased sensitivity to the inhibitory effects of circulating glucocorticoids on post-stress hypothalamic-pituitary-adrenal activity. Both effects persist throughout life. The effects of handling on type II corticosteroid receptor development are, at least in part, mediated by changes in hippocampal 5-hydroxytryptamine turnover. Moreover, 5-hydroxytryptamine can regulate type II corticosteroid receptor density in cultured hippocampal cells, providing a paradigm for examining the neurochemical mechanisms by which environmental stimuli might regulate neural differentiation. In the present studies, we examined the intracellular mechanisms underlying the effects of 5-hydroxytryptamine on type II corticosteroid receptors ([3H]RU 28362 binding) in hippocampal cell cultures. cAMP, but not cGMP, levels in cultured hippocampal cells were significantly increased by the addition of 5-hydroxytryptamine to the medium. The cAMP response to 5-hydroxytryptamine was biphasic: an initial increase in cAMP levels occurred in response to nanomolar 5-hydroxytryptamine concentrations (EC50 = 7.2 nM), while a second increase was apparent at low micromolar concentrations. 5-Hydroxytryptamine also increased [3H]RU 28362 binding (EC50 = 4.5 nM) with a maximal effect at a concentration of 10 nM. There was no further increase in [3H]RU 28362 binding even with higher, micromolar concentrations of 5-hydroxytryptamine.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Adrenal phenylethanolamine N-methyltransferase induction in relation to glucocorticoid receptor dynamics: evidence that acute exposure to high cortisol levels is sufficient to induce the enzyme.

Glucocorticoids (GCs) are thought to regulate, in a permissive fashion, the basal activity of adrenal medullary phenylethanolamine N-methyltransferase (PNMT). However, it is unclear whether a large short-term increase in GC release, such as occurs during an acute stress response, may also play a role in PNMT regulation. The present study investigated how the GC influence over PNMT activity varies in relation to dynamic changes in the hormone-receptor signal. Using [3H]dexamethasone (DEX) and [3H]RU 28362 as radioligands, we have confirmed the presence of GC receptors in bovine adrenal medullary cells. A concentration-dependent decline in soluble GC receptor sites and an increase in nuclear uptake of [3H]DEX were found in response to GC levels as low as 5 x 10(-8) M. The loss of soluble sites plateaued between 5 x 10(-8) and 10(-6) M cortisol, with further losses occurring at 10(-5) and at 10(-4) M. The functional consequence of GC receptor binding was confirmed by measuring PNMT activity following 3-day exposure to cortisol. The pattern of PNMT induction was similar to that seen with GC receptor occupancy; at cortisol concentrations between 10(-8) and 10(-5) M, PNMT induction was at a plateau, with a further increase in activity at 10(-4) M. The increase in PNMT activity following 3-day exposure to low (10(-7) M) and high (5 x 10(-5), 10(-5) M) cortisol was blocked by the GC receptor antagonist RU 38486, suggesting a GC receptor-mediated event. Finally, a short (2 h) pulse of GC, which mimics the time course of physiological elevation of GC following acute stress, elevated adrenal medullary PNMT activity measured 3 days later. Therefore, our results provide novel evidence that short-term exposure of adrenal medullary cells to high cortisol levels can elevate PNMT activity.

Adrenal Medulla↗
PubMed1992

Basal ACTH, corticosterone and corticosterone-binding globulin levels over the diurnal cycle, and age-related changes in hippocampal type I and type II corticosteroid receptor binding capacity in young and aged, handled and nonhandled rats.

Basal corticosterone (B) levels increase with age in the rat, a result of decreased negative-feedback inhibition of hypothalamic-pituitary-adrenal (HPA) activity. Postnatal handling increases CNS negative-feedback sensitivity and appears to attenuate some of the changes occurring in the HPA axis in later life. In the experiments described here, we have examined basal HPA function in young (6-8 months) and old (22 months), handled (H) and nonhandled (NH) rats in relation to changes in corticosteroid receptor binding. Among young animals, there were no group differences in basal adrenocorticotropin (ACTH) or B levels at any point in the diurnal cycle. In contrast, plasma ACTH and B levels during the PM phase were significantly higher in old NH animals in comparison to old H animals and to both groups of young animals. The H and NH groups did not differ in in vivo adrenal responsiveness to exogenous ACTH. As expected, ACTH sensitivity was greater in all groups during the PM phase and in general, old animals showed a greater response to ACTH regardless of the treatment group. There were no differences across the groups in AM plasma corticosterone-binding globulin (CBG) levels. However, during the PM phase of the cycle, CBG levels were significantly lower and the percentage of B in the free form was significantly higher in the old NH animals. As expected, levels of free B during the PM phase of the cycle were significantly higher in the old NH animals. Thus, there is a significant increase in the PM corticoid signal in the old NH animals that occurs as a function of elevated B and decreased CBG levels; these age-related changes in basal HPA activity were not seen in the old H animals. Type I (mineralocorticoid-like) receptor binding in the hippocampus did not differ as a function of handling and was significantly reduced with age in both H and NH animals. Type II (glucocorticoid) receptor binding decreased as a function of age in both H and NH animals, but was consistently higher in the H animals. There were no differences in type II receptor binding in the hypothalamus or pituitary as a function of age or handling. These data suggest that the increase in basal HPA activity occurring in aged rats is largely restricted to the dark phase of the cycle and is attenuated by postnatal handling, a treatment that increases hippocampal type II corticosteroid receptor binding.

Adrenocorticotropic Hormone↗
PubMed1991

The effects of neonatal handling on the development of the adrenocortical response to stress: implications for neuropathology and cognitive deficits in later life.

Several years ago Levine, Denenberg, Weininger, Ader, and others described the effects of postnatal "handling" on the development of behavioral and endocrine responses to stress. The handling procedure usually involved removing rat pups from their cages, placing the animals together in small containers, and 15-20 min later, returning the animals to their cages and their mothers. The manipulation was performed daily for the first 21 days of life. As adults, handled (H) rats exhibited attenuated fearfulness (e.g., decreased freezing, increased exploration) in novel environments and a less pronounced increase in the secretion of adrenal glucocorticoids in response to a variety of stressors. These findings clearly demonstrated that the development of rudimentary, adaptive responses to stress could be modified by environmental events. We have followed on these earlier handling studies, convinced that this paradigm provides a marvelous opportunity to examine how subtle variations in the early environment alter the development of specific biochemical systems in the brain, leading to stable individual differences in biological responses to stimuli that threaten homeostasis. In this work we have shown how early handling influences the neurochemical development of certain brain regions that regulate the adrenocortical response to stress. Neonatal handling increases the efficiency of this endocrine response to stress, preventing excessive exposure to the highly catabolic adrenal steroids. In later life, this effect appears to protect the animal from potentially damaging effects of these steroids, ensuring the anatomical integrity of brain structures involved in cognitive functioning.

Adrenal Cortex↗
PubMed1991

Cellular mechanisms underlying the development and expression of individual differences in the hypothalamic-pituitary-adrenal stress response.

Several years ago Levine, Denenberg, Ader, and others described the effects of postnatal "handling" on the development of behavioral and endocrine responses to stress. As adults, handled rats exhibited attenuated fearfulness in novel environments and a less pronounced increase in the secretion of the adrenal glucocorticoids in response to a variety of stressors. These findings clearly demonstrated that the development of rudimentary, adaptive responses to stress could be modified by environmental events. We have followed these earlier studies, convinced that this paradigm provides a marvellous opportunity to examine how subtle variations in the early environment alter the development of specific neurochemical systems, leading to stable individual differences in biological responses to stimuli that threaten homeostasis. In this work we have shown how early handling influences the development of certain brain regions that regulate glucocorticoid negative-feedback inhibition over hypothalamic-pituitary-adrenal (HPA) activity. Specifically, handling increases glucocorticoid (type II corticosteroid) receptor density in the hippocampus and frontal cortex, enhancing the sensitivity of these structures to the negative-feedback effects of elevated circulating glucocorticoids, and increasing the efficacy of neural inhibition over ACTH secretion. These effects are reflected in the differential secretory pattern of ACTH and corticosterone in handled and nonhandled animals under conditions of stress. In more recent years, using a hippocampal cell culture system, we have provided evidence for the importance of serotonin-induced changes in cAMP levels in mediating the effect of postnatal handling on hippocampal glucocorticoid receptor density. The results of these studies are consistent with the idea that environmental events in early life can permanently alter glucocorticoid receptor gene expression in the hippocampus, providing evidence for a neural mechanism for the development of individual differences in HPA function.

Animals↗
PubMed1991

Effects of corticosterone on response consolidation and retrieval in the forced swim test.

In the forced swimming test, adrenal hormones regulate immobility time during a test swim given 24 hr after the initial training swim (e.g., the deficit in adrenalectomized animals is reduced when animals are given corticosterone [B] immediately after the training session). In this study, adrenalectomy decreased and B restored immobility during the test swims. The effects of adrenalectomy were completely reversed by 1 mg/kg doses of B, which results in plasma B levels that are comparable to values under basal resting conditions. Higher doses of B had no further effect. B given before or immediately after training partially reversed the effects of adrenalectomy. The complete reversal of the effects of adrenalectomy, however, required the presence of B during both training and testing, suggesting that B plays a role in the consolidation-retention and retrieval of the immobility response.

Adrenalectomy↗
PubMed1991

Variations in the hypothalamic-pituitary-adrenal response to stress during the estrous cycle in the rat.

To investigate the role of gonadal steroids in the hypothalamic-pituitary-adrenal (HPA) response to stress, we studied adrenocorticotrophin (ACTH) and corticosterone (B) responses to 20-min restraint stress in cycling female rats, and in ovariectomized (OVX) rats replaced with physiological levels of estradiol (E2) and progesterone (P). In cycling rats, we found significantly higher peak ACTH (P less than 0.01) and B (P less than 0.05) responses to stress during proestrus compared to the estrous and diestrous phases. No differences were found in either basal ACTH and B levels across the cycle phases. In a separate study, OVX rats were maintained on low, physiological levels of E2 and P with silastic implants for 3 days, and injected either with oil (O'), 10 micrograms of E2 (E') 24 h before stress testing, or with E2 and 500 micrograms P 24 and 4 h, respectively, prior to stress (EP'). These treatments mimicked endogenous profiles of E2 and P occurring during diestrous, proestrous, and late proestrous-early estrous phases, respectively. In response to stress, ACTH levels were higher (P less than 0.01) in the E' group compared to the EP' and O' groups. Although the peak B response was similar in all groups, the E' and EP' groups secreted more B after the termination of stress than did the O' group. Within the 20 min stress period, ACTH levels in the E' group were significantly (P less than 0.05) higher at 5, 10, and 15 min after the onset of stress, compared to the EP' and O' groups. Plasma B levels were significantly higher in the E' group at 5 and 10 min (P less than 0.05 and P less than 0.01, respectively) compared to the EP' and O' group. beta-endorphin-like immunoreactive responses to restraint stress were also significantly higher in the E' group compared to the EP' (P less than 0.05) and O' (P less than 0.01) groups. In contrast to the effect seen at 24 h, ACTH responses to stress 48 h after E2 injection in the E' group were comparable to O' animals. There was no effect of E2 on ACTH clearance, whereas B clearance was enhanced in E' treated animals vs. O'-treated animals. These results indicate that the HPA axis in the female rat is most sensitive to stress during proestrous. Such enhanced HPA responses to stress are limited to the early portion of proestrous, as progesterone appears to inhibit the facilitatory effects of estrogen on ACTH release during stress. Taken together, these results suggest an ovarian influence on both activational and inhibitory components of HPA activity.

Adrenocorticotropic Hormone↗
PubMed1990

The role of serotonin in the development and environmental regulation of type II corticosteroid receptor binding in rat hippocampus.

Hippocampal concentrations of serotonin (5-HT) increase over the first two weeks of life, and show a peak on day 14. This pattern is very similar to the previously reported developmental changes in hippocampal type II corticosteroid receptor binding. We found that adult animals treated during the first days of life with the 5-HT neurotoxin, 5.7-dihydroxytryptamine, showed reduced hippocampal type II corticosteroid receptor binding. In addition, manipulations that resulted in increased hippocampal type II corticosteroid receptor binding, such as neonatal handling or exogenous thyroid hormone treatment also increased hippocampal 5-HT turnover. Finally, concurrent administration of the 5-HT2 receptor antagonist, ketanserin, blocked the effects of handling on hippocampal type II corticosteroid receptor binding. Taken together with the results of recent in vitro experiments, these data suggest that (a) 5-HT may be involved in the ontogenetic variation in hippocampal type II corticosteroid receptor binding, and (b) that increases in 5-HT activity may mediate the effects of environmental stimulation on hippocampal type II corticosteroid receptor binding.

5,7-Dihydroxytryptamine↗
PubMed1990

Androgen binding sites in human temporal cortex.

We have characterized putative androgen receptor binding sites in five separate biopsy samples of human temporal cortex from epilepsy patients using an in vitro exchange assay with soluble fractions and [3H]5 alpha-dihydrotestosterone as radioligand. The results revealed highly specific, saturable binding with an apparent affinity constant (Kd) of approximately 2 nM with a moderate capacity (Bmax) of approximately 50 fmol/mg protein. In competition studies, we found that only testosterone and 5 alpha-dihydrotestosterone competed effectively (i.e. at low nanomolar concentrations) for [3H]5 alpha-dihydrotestosterone binding sites. These data indicate the presence of androgen receptors in human cortex that are pharmacologically very similar to that previously described in rodent and infrahuman primate CNS, and suggest the existence of a possible mechanism whereby circulating androgens might influence neuronal events in human cortex.

Adolescent↗
PubMed1990

Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats.

There is a tendency for increased hypothalamic-pituitary-adrenal (HPA) activity with age in the rat, and the resulting elevations in circulating glucocorticoid levels have been implicated in the occurrence of hippocampal pathology and memory deficits. In the experiments reported here, we examined whether HPA dysfunction is selectively associated with cognitive impairments in a population of aged rats. Fifty-eight 23-27-month-old male Long-Evans rats were screened for spatial memory impairments using the Morris swim maze, and 2 groups of aged animals were selected; aged, cognitively impaired (AI) animals whose performance was significantly different (greater than 2 SD) from that of 6-month-old controls and aged, cognitively unimpaired (AU) animals whose performance was comparable to that of the young controls (a difference of less than 0.5 SD). Twenty-eight percent of the animals tested were designated as AI and 20% as AU. Histological analysis of a subset of these animals showed that, while both AU and AI animals showed neuron loss in the pyramidal cell fields of the hippocampus, the loss was significantly greater in the AI animals. The AI animals showed clear evidence of increased HPA activity. Thus, basal ACTH and corticosterone levels were significantly higher in the AI animals compared with both AU animals and young controls, especially during the dark phase of the cycle. The AI, AU, and young animals exhibited comparable corticosterone levels during a 20-min immobilization stress; however, following the termination of the stressor, corticosterone levels in AI animals were significantly elevated compared with both AU animals and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1990

Serotonin regulates type II corticosteroid receptor binding in hippocampal cell cultures.

Previous work from our laboratory has shown that early postnatal handling of rat pups permanently increases hippocampal type II, but not type I, corticosteroid receptor binding. Handling also increases hippocampal 5-HT turnover, and the effect of handling on type II corticosteroid receptor binding is blocked by concurrent administration of the 5-HT2 receptor antagonist ketanserin. In view of these findings, the present studies examined the effects of 5-HT on type I ([3H]corticosterone) and type II ([3H]RU 28362) corticosteroid receptor binding in dispersed hippocampal cell cultures derived from animals killed at E19-20 in order to verify that 5-HT can act directly on hippocampal cells to alter corticosteroid receptor binding. Both type I and type II receptors were measurable in cultured hippocampal cells and the apparent affinity (Kd) for [3H]corticosterone (0.4 +/- 0.1 nM) and [3H]RU 28362 (0.8 +/- 0.1 nM) was similar to that from studies with intact animals. 5-HT increased type II, but not type I, corticosteroid receptor binding capacity in a dose-related manner, with the maximal effect (+188%) observed at 10 nM 5-HT and no change in the affinity of the receptor for [3H]RU 28362. The effect of 10 nM 5-HT on [3H]RU 28362 binding required a minimum of 4 d exposure and persisted for at least 7 d following the removal of 5-HT. The effect of 10 nM 5-HT on [3H]RU 28362 binding was completely blocked by the 5-HT2 receptor antagonists ketanserin and mianserin. There were no effects of the 5-HT1a antagonist, BMY 7378, or the 5-HT3 antagonist, MDL 72222.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: relationship to presynaptic cholinergic markers and binding sites.

The main objective of the present work was to determine whether the regulation of ACh release by nicotinic and muscarinic autoreceptors is compromised in the aged rat brain. For this, the effects of the nicotinic agonist N-methylcarbamylcholine (MCC) and the muscarinic-M2 antagonist AF-DX 116 on ACh release from brain slices of young (3-month-old), adult (9-month-old), and aged (27-month-old) rats were tested. The ability of MCC to enhance spontaneous ACh release in hippocampal, cerebral cortical, and cerebellar slices was only modestly altered with age. In contrast, the sensitivity of muscarinic autoreceptors in the aged hippocampus and cerebral cortex, but not the striatum, to blockade by the muscarinic-M2 antagonist AF-DX 116 was severely attenuated. To assess whether the age-related changes in cholinergic autoreceptor function may be due to deficits in presynaptic cholinergic markers, we tested whether choline acetyltransferase (ChAT) activity, basal and evoked ACh release, and nicotinic and muscarinic binding sites are altered in the aged rats. ChAT activity in forebrain regions was decreased in the aged compared to the young and mature adult rats. Furthermore, the potassium-evoked, but not the spontaneous, release of ACh was markedly depressed in striatal, hippocampal, and cortical slices of aged rats. The densities of nicotinic and muscarinic-M2 binding sites, assessed using 3H-MCC and 3H-AF-DX 116 as selective ligands, respectively, were markedly reduced in homogenates of the striatum, hippocampus, cerebral cortex, and thalamus of aged rats. In contrast, muscarinic-M1 sites, selectively labeled with 3H-pirenzepine, were not affected. Therefore, it appears that age-related decrements in ChAT activity and in muscarinic-M2, but not nicotinic, binding sites in the rat brain are reflected in a decreased function of muscarinic-M2 autoreceptors. However, the positive correlation between loss of ChAT activity, decreased muscarinic-M2 binding sites, and impaired muscarinic autoreceptor function is clearly tissue dependent.

Acetylcholine↗
PubMed1989

A comparison of the effects of diazepam versus several typical and atypical anti-depressant drugs in an animal model of anxiety.

We examined the anxiolytic effects of a variety of anti-depressant drugs, administered either acutely or chronically, in an animal model of anxiety involving novelty-suppressed feeding in food-deprived rats. Following a single injection of desipramine (10 mg/kg) amitriptyline (10 mg/kg), mianserin (10 mg/kg), fluoxetine (10 mg/kg), buspirone (4 mg/kg), gepirone (4 mg/kg) or nomifensine (10 mg/kg), there was no decrease in the latency to begin eating in the novel environment such as occurred with diazepam (2 mg/kg). In fact, an increased latency was observed for desipramine, amitriptyline, fluoxetine, and nomifensine. In contrast, chronic (21 days) treatment with each of the above-mentioned drugs, except nomifensine, significantly reduced the latency to begin eating relative to vehicle controls. These findings suggest that a variety of tricyclic and novel anti-depressant drugs acquire anxiolytic properties following chronic administration.

Animals↗
PubMed1989

Glucocorticoid receptors in brain and pituitary of the lactating rat.

The female rat exhibits elevated corticosterone levels throughout lactation, suggesting a possible dampening of the sensitivity of adrenocortical negative-feedback processes during this period. Negative-feedback within the adrenocortical axis is, in large part, mediated by an enhanced hormone receptor signal at a number of glucocorticoid target sites, including the pituitary, hypothalamus, and hippocampus. In the study reported here we have measured glucocorticoid receptor binding capacity in soluble fractions prepared from these tissues, using an in vitro binding assay with [3H]dexamethasone as radioligand. We found that during at least the first two weeks of lactation the rat shows significantly decreased [3H]dexamethasone binding capacity in the hippocampus, with no change in pituitary or the hypothalamus during lactation. These data provide one possible mechanism whereby a critical target region for adrenocortical negative-feedback might be desensitized to circulating glucocorticoids, thus permitting the sustained elevation in pituitary-adrenal activity.

Adrenal Cortex↗
PubMed1989

Role of the central benzodiazepine receptor system in behavioral habituation to novelty.

In this article we report the results of two experiments examining the role of central benzodiazepine receptor sites in the response to novelty. Animals that were food deprived and presented with food in a novel environment showed long latencies before they began eating. Pretreatment with diazepam or preexposure to the "novel" environment for 1 hr/day for 4 or 7 days before testing in that environment dramatically reduced the latency to begin eating. Administration of either the "inverse agonist," FG-7142, or an antagonist, RO15-1788, of the central benzodiazepine receptor before testing completely reversed the effects of 7 days of preexposure to the novel environment. In home-cage feeding tests, FG-7142, but not RO15-1788, increased the latency to begin feeding in food-deprived animals. These findings indicate that FG-7142 is strongly anxiogenic, whereas RO15-1788 is not anxiogenic, yet both drugs are potent in reversing the effects of habituation. The results of these experiments suggest that the normal process of habituation to novelty may involve the release of an endogenous, anxiolytic compound (an agonist) that binds to a central benzodiazepine receptor, the effects of which are blocked by RO15-1788.

Animals↗
PubMed1989

Neonatal handling alters adrenocortical negative feedback sensitivity and hippocampal type II glucocorticoid receptor binding in the rat.

Adult rats handled (H) daily for the first 3 weeks of life show a dramatically altered adrenocortical response to stress. We found that H animals secreted less ACTH and corticosterone (B) during and following the termination of stress than did nonhandled (NH) controls. In contrast, H and NH animals did not differ in basal B secretion at any point in the diurnal cycle, nor in adrenocortical responses to exogenously administered oCRF or ACTH. Moreover, the clearance rate for B was similar in H and NH animals. H animals were more sensitive than NH animals to the inhibitory effects of either B or dexamethasone on stress-induced adrenocortical activity. In a dose-response study, both glucocorticoids administered 3 h prior to testing suppressed the adrenocortical response to a 20-min restraint stress to a greater extent in the H animals. Handling increased type II, glucocorticoid receptor binding capacity in the hippocampus of adult animals (approximately 50% increase in capacity, with no change in affinity). There were no handling-induced changes in type II receptor binding capacity in the hypothalamus or pituitary, nor in type I receptor binding capacity in the hippocampus. Following chronic (5 mg/kg/day) treatment with B, hippocampal type II receptor binding capacity was significantly reduced in the B-treated H animals, compared with saline-treated H animals, and indistinguishable from saline-treated NH animals. Down-regulated H animals, like NH animals, hypersecreted B following the termination of stress in comparison to the saline-treated H animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1989

Differential activation of the pituitary-adrenocortical axis after stress in the rat: use of two genetically selected lines (Roman low- and high-avoidance rats) as a model.

We have examined the activation of the pituitary-adrenal axis in two lines of rats, the Roman high (RHA)- and low (RLA)-avoidance rats known to be emotionally different. These rats are selected for rapid acquisition of a conditioned avoidance response (RHA) compared with failure to acquire this response (RLA). In this study the endocrine response (ACTH, corticosterone, aldosterone) of RLA and RHA rats to two types of stress was examined: exposure to open-field stress for 10 min (Op) or exposure to ether vapours for 3 min (E). Basal plasma ACTH concentrations were lower in RLA than in RHA rats (RLA: 110.8 +/- 24.5 ng/l; RHA: 252.7 +/- 60.8 ng/l, P less than 0.05) but the absolute values of ACTH reached after both types of stress were comparable between RLA and RHA rats. Plasma corticosterone and aldosterone under resting conditions were not different between RLA and RHA rats. Plasma corticosterone was higher in RLA following openfield stress (P less than 0.05) while no differences between RLA and RHA were observed after ether stress (RHA: basal = 66 +/- 14.nmol/l, Op = 384 +/- 55, E = 606 +/- 75; RLA: basal = 121 +/- 52, Op = 612 +/- 92, E = 698 +/- 89). Stress-induced increases in plasma aldosterone were higher in the RLA line after both types of stress (RHA: basal = 175 +/- 36 pmol/l, Op = 546 +/- 53, E = 563 +/- 47; RLA: basal = 272 +/- 64, Op = 1246 +/- 91, E = 863 +/- 72).

Adrenal Cortex↗