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Colchicine blockade of axonal transport from the paraventricular nucleus to the median eminence was used to indirectly infer ACTH secretagog release in response to the psychological stressors of social interactions and various degrees of novelty. Placing a rat in a new cage with either the smell or presence of a novel conspecific decreased arginine vasopressin and oxytocin (OT) contents, but not corticotropin-releasing factor content. Secretagog contents were unchanged in rats in their home cages faced with a novel conspecific. Secretagog release during social stress is thus primarily a function of being in a novel setting. For different degrees of novelty, rats were placed in either a novel cage, a novel bucket, or a novel bucket smelling of another rat. Whereas secretagog contents were unchanged with a novel cage, OT content alone decreased in response to both the bucket and the unclean bucket. Despite a graded corticosterone response, there was no distinction in the OT response, suggesting that the colchicine technique cannot accurately reflect gradations of stressors.
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PMID:Patterns of adrenocorticotropin secretagog release in response to social interactions and various degrees of novelty. 789 37

The effect of stress to the pregnant mother on hormonal responses of the offspring to stressful events was investigated in juvenile rhesus monkeys. Six pregnant monkeys were repeatedly removed from their home cages and exposed to unpredictable noise during mid- to late gestation (Days 90-145 postconception), while six undisturbed pregnant mothers served as controls. Blood samples were collected from the juvenile offspring under anesthesia on four occasions and assayed for ACTH and cortisol. In a second experiment, blood samples were collected from the awake offspring under a baseline and four progressively stressful conditions. Offspring of stressed mothers showed higher ACTH and cortisol levels than control offspring at all four anesthesia samples and at a nonanesthesized home cage baseline. Prenatally stressed offspring also showed higher ACTH values in all four stress conditions. Cortisol values were similar for the two groups under the stress conditions. The disparity between the two groups in the relationship between ACTH and cortisol was greatest in the most stressful condition, suggesting regulatory differences between the two groups. These results indicate that offspring of primate mothers stressed during pregnancy show enhanced HPA axis responsivity to stressors later in life, and concur with rodent findings indicating that prenatal stress may have long-term effects on HPA axis regulation.
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PMID:Long-term effects of prenatal stress on HPA axis activity in juvenile rhesus monkeys. 792 79

To determine the cell groups which are activated by novelty stress, we examined the induction of c-fos mRNA in brain tissues following introduction of male rats to a novel open field. Male Fischer 344 rats were placed in a brightly lit open field and allowed to roam free for 20 min. Control animals were sacrificed upon removal from their home cage. Northern blot analysis revealed a 2.2 kb hybridization signal which increased in density following novelty. In situ hybridization analysis showed that c-fos mRNA was induced in a specific pattern consistent with the behavior. The regions of induction included the medial prefrontal and orbital cortex, cingulate and parietal cortex, hippocampal CA1 and CA3 pyramidal cell regions, dorsal and ventral anterior thalamic n. and paraventricular n. of the hypothalamus. C-fos mRNA also increased in the anterior pituitary gland and this increase correlated with the secretion of ACTH. These data demonstrate the brain areas undergoing genomic activation following complex behavior paradigms such as introduction to a novel environment.
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PMID:Induction of c-fos mRNA in the brain and anterior pituitary gland by a novel environment. 821 31

One-week exposure to crowding stress has been reported to affect body weight and pituitary-adrenal axis activity. This study has first evaluated whether the aforementioned changes are associated with altered exploratory activity. One-week crowding (16 rats/cage) diminished body weight gains, compared to the control situation (four rats/cage): actually, this difference was mainly due to a marked loss in food intake and body weight following the first day of crowding. On the other hand, 1-week crowded rats were not different from their controls when placed for the first time in an open field, as shown by the analysis of their exploratory activities, their number of grooming episodes, and their defecation. Psychoneuroendocrine effects of 1-day crowding were then investigated: actually, open field behaviors were not modified but basal plasma glucose levels were decreased. Moreover, neither plasma ACTH and corticosterone levels nor 2-min cold swim-induced increases in corticosterone levels were affected. Besides, cold swim-induced increases in plasma ACTH levels were amplified in crowded rats, and these increases were associated with hyperglycemia in crowded, but not in control rats. It is suggested that 1-day exposure to crowding has differential consequences upon feeding and exploratory behaviors while potentiating the responsiveness of stress hormones.
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PMID:Psychoneuroendocrine outcomes of short-term crowding stress. 824 55

Previous studies have found evidence of behavioral and psychophysiological differences between nonhuman primates reared in different social environments, however, few of these have employed longitudinal study of the animals over early development. In this study, HPA axis activity was assessed via measurement of ACTH and cortisol values over the first 6 months of life and in response to two stressful housing transitions in 48 infant rhesus monkeys that were either mother- or peer-reared. ACTH and cortisol values declined over the first 6 months in both rearing groups. Peer-reared monkeys showed lower levels of ACTH over the first 6 months of life than mother-reared, but the rearing groups did not differ in basal cortisol values over this period. Mother-reared animals showed a greater ACTH response to the mild stress of being moved to a new cage, and male monkeys showed higher values than females. Mother-reared animals showed the largest cortisol increase in response to the caging transition. Both groups showed increases in ACTH and cortisol in response to the more severe stress of separation from their rearing partners and housing with unfamiliar age-mates. Mother-reared animals again showed the largest increase in ACTH in response to these events, but increases in cortisol were similar among both sexes and rearing groups. These results suggest an interaction of sex and rearing history in response to stressful events.
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PMID:Social rearing effects on HPA axis activity over early development and in response to stress in rhesus monkeys. 829 90

The present study investigated the question of how restraint affects the hypothalamo-pituitary adrenocortical axis and the hypothalamo-pituitary gonadal axis in intact, adult female rhesus macaques in both the follicular and luteal phases of the menstrual cycle. Restraint was chosen because it is not physically harmful to the animal but rather serves primarily as a psychological stressor. Blood samples were collected from a remote site at 15-min intervals beginning at 0700 h from tethered adult female rhesus macaques. Each animal was subjected to 6 h of chair restraint after a 3-h control period in the animal's home cage. Samples were collected for an additional 6 h after the end of the restraint period, when each animal was returned to its home cage. Brief anesthesia with ketamine (administered through indwelling catheter) facilitated transfer of the animals to and from the chair. Blood samples were also collected from undisturbed females in both the follicular and luteal phases to document LH, cortisol, and progesterone secretion throughout the day. Plasma ACTH and cortisol, measured as indices of stress, were elevated within 15 min after initiation of restraint and remained elevated after the animals were returned to their cages. In animals sampled in the follicular phase, mean plasma LH levels were lower during restraint and remained suppressed for several hours after the animals were removed from restraint. LH levels were not significantly inhibited by restraint in the luteal phase. When the opiate receptor antagonist naloxone (Nx; 5 mg bolus plus 5 mg/h) was given beginning 2 h after the initiation of restraint, LH levels were elevated compared to prerestraint levels in both phases of the menstrual cycle. These data indicate that restraint is a potent activator of the pituitary-adrenal axis and that at least in the follicular phase of the menstrual cycle, restraint inhibits pituitary LH release. This inhibition of gonadotropin release may involve endogenous opiate suppression of GnRH release, since Nx reversed the effect of restraint.
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PMID:Restraint inhibits luteinizing hormone secretion in the follicular phase of the menstrual cycle in rhesus macaques. 831 40

We examined the biologic properties of a small-cell-lung-carcinoma (SCLC) cell line (designated MN-1112) established from a patient with SCLC who showed paraneoplastic retinopathy syndrome. Morphologic and immunocytochemical analyses showed that MN-1112 cells possess features of the classic type of SCLC. MN-1112 cells grew in suspension forming relatively large clumps of cells with a doubling time of 72 hr. By light-microscope examination, the cells were relatively small and had scanty cytoplasm. The cells produced NSE, ACTH and CK (BB isozyme); they also expressed recoverin, a novel photoreceptor protein, detected by Northern-blot and Western-immunoblot analysis using human-recoverin-specific DNA probe and anti-bovine-recoverin polyclonal antibody. This report shows that human recoverin is expressed in cultured SCLC cells. Our results support the hypothesis that, in cancer-associated retinopathy (CAR) patients, auto-immune antibody targeting for ectopic recoverin in SCLC is initially produced and cross-reacts with the retinal protein, resulting in the retinal degeneration that occurs in CAR patients.
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PMID:Characterization of a small-cell-lung-carcinoma cell line from a patient with cancer-associated retinopathy. 859 20

Previous work from our laboratory provided evidence for increased plasma corticosterone levels in mice transgenic for human and bovine growth hormone (GH). Corticosterone was elevated in both sexes, under both basal and ether-induced stress conditions. The objectives of the present study were to investigate the in vitro adrenal sensitivity to ACTH, GH and/or IGF-I in normal and bGH transgenic mice, to examine plasma corticosterone levels at different times of the day, and to determine plasma levels of ACTH in these animals. For the measurement of plasma corticosterone and ACTH levels, transgenic and normal siblings were housed 2 per cage and decapitated simultaneously within 20 seconds of the first disturbance of the cage. The corticosterone production by in vitro adrenal incubations did not differ between adrenals from normal and transgenic mice at the basal level or in the presence of different doses of ACTH. Growth hormone or IGF-I did not have any effect on corticosterone production in vitro when given alone, and did not modify the effects of ACTH on the accumulation of corticosterone production in vitro when alone, and did not modify the effects of ACTH on the accumulation of corticosterone in the media. Plasma corticosterone concentrations were higher in transgenic than in normal animals in both morning and evening. Plasma concentrations of ACTH in animals killed in the morning were sharply increased in transgenic males as compared with their normal siblings. The results indicate that increased circulating levels of corticosterone in transgenic mice are not due to a potentiation of ACTH actions by GH or IGF-I, but rather to a chronic increase in plasma ACTH levels. The increase in ACTH is presumably a reflection of GH actions in the hypothalamic-pituitary system.
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PMID:Increased plasma corticosterone levels in bovine growth hormone (bGH) transgenic mice: effects of ACTH, GH and IGF-I on in vitro adrenal corticosterone production. 867 46

To elucidate some of the mechanisms underlying the neuroendocrine and neurochemical changes associated with age in female rats, we administered the serotonin (5-HT) releaser and reuptake inhibitor, d-fenfluramine (d-FEN; 0.0 or 0.6 mg/kg/day, PO) for 30-38 days to young (4 month) and old (21 month) F-344 female rats. Animals were placed into a novel open field (OF) for 20 min before sacrifice. Control animals were sacrificed immediately upon removal from their home cage (HC). Old rats exhibited significantly (p < 0.05) less exploratory behavior and a smaller CORT response to OF than young animals. d-FEN treatment had no effect on plasma ACTH and CORT levels or exploratory behavior. The old HC rats had significantly (p < 0.05) higher plasma levels of prolactin (PRL) than the young HC rats. A stress induced increase in PRL secretion was observed in the old rats only, which was attenuated by d-FEN treatment. In the OF groups, both the young and old rats showed elevated medial frontal cortex (MFC) dopamine turnover (DOPAC/DA ratio), but only the young rats exhibited an elevation in norepinephrine (NE) turnover (MHPG/NE ratio). d-FEN treatment blocked the stress-induced increase in NE turnover in the young rats and the increase in DA turnover in the old rats. These data suggest that 5-HT activity could be involved in the age-related changes in the MFC catecholamine and PRL responses to stress in female rats.
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PMID:Responses to novelty stress in female F344 rats: effects of age and d-fenfluramine treatment. 886 67

The purpose of the present study was to evaluate the role of central alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate type of glutamate receptors in the control of ACTH and corticosterone release under basal and stress conditions. AMPA/ kainate competitive receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX), which does not penetrate the blood-brain barrier, was administered intracerebroventricularly (i.c.v.). A modified method for i.c.v. drug administration in conscious freely moving rats was employed. DNQX or artificial cerebrospinal fluid (aCSF) was injected into lateral ventricle through a thin polyethylene cannula with a steel needle on the end which was inserted and moved via large polyethylene cannula to the guide stainless steel cannula. This procedure was performed out of the cage. ACTH and corticosterone release under basal conditions and during immobilization stress were investigated. Intracerebroventricular administration of DNQX resulted in an increase of ACTH and corticosterone in plasma reaching maximal values at 15 min after drug injection. During immobilization stress, i.c.v. DNQX induced a mild reduction in plasma ACTH levels compared to those in aCSF pretreated rats. Corticosterone secretion was high throughout the whole period of stress exposure. These findings indicate that endogenous excitatory amino acids (EAA) acting at AMPA/kainate receptors may interfere with the control of ACTH release under both basal and stress conditions, but the mechanisms involved remain to be elucidated.
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PMID:Effect of central administration of the non-NMDA receptor antagonist DNQX on ACTH and corticosterone release before and during immobilization stress. 937 80


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