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Biomedical subjects

S Levine

Publications and source records attributed to S Levine.

At least 397 records · Page 22Linked to original sources

Sex differences in biobehavioral responses to conflict in a taste aversion paradigm.

A conditioned aversion to a novel milk solution was produced, and animals were then reexposed to milk while nondeprived (low conflict) or following a 72-hr food and water deprivation regimen (high conflict). No sex differences occurred if animals were nondeprived throughout testing. However, if deprived during the interval between conditioning and reexposure, sex differences in both behavior and adrenocortical responses occurred: (1) Presession corticoid levels of females were higher than those of males. (2) On the first reexposure day, females showed a suppression of plasma corticosterone below presession levels, while males maintained elevated or increased corticosterone levels. (3) On the second reexposure day, when no longer deprived, males showed a marked suppression of intake compared to females, and females subsequently recovered to pretoxicosis intake levels faster than males. (4) Gonadectomy eliminated these sex differences. While ovariectomized females continued to resemble intact females in both behavioral and hormonal responses, castrated males exhibited a corticoid suppression on the first reexposure day, and subsequently recovered to pretoxicosis intake levels at the same rate as females.

Animals↗

Hormonal responses accompanying fear and agitation in the squirrel monkey.

The adrenocortical and gonadal responses of 14 male monkeys were evaluated during four experimental conditions in order to evaluate the influence of social interactions on endocrine responsiveness. Plasma hormone levels were determined during the establishment of social relations, after 60-min exposures to a novel environment, after 60-min exposures to a snake, and 60 min after ACTH administration. Both adrenal and gonadal secretion changed significantly during the first day after social relations were established, although only dominant males showed increases in testosterone, whereas cortisol levels rose in all subjects. Increases in cortisol, but not testosterone, were also observed following exposure to novelty or a snake. The presence of a social partner reduced signs of behavioral disturbance during these test conditions, although the adrenal responses were equivalent or greater than when tested alone. This finding qualifies earlier research which indicated that social support was beneficial for reducing stress when squirrel monkeys were tested in larger groups in their home environment.

Adrenocorticotropic Hormone↗

Cortisol responses under different housing conditions in female squirrel monkeys.

Adult female squirrel monkeys were housed in a group, in pairs or individually. Plasma levels of cortisol obtained under basal and stress conditions once weekly for four weeks were significantly lower in pair-housed females than in those living in a social group or individually. The increment in cortisol levels after stress (induced by handling and ether anesthesia) also was smaller in females housed in pairs. The cortisol values of the pair-housed females were positively correlated with those of their partners. Basal cortisol levels in the group-living females showed a significant rank-order correlation with dominance status. This indicated that social interactions in group-living animals can influence cortisol levels in a complex manner, either increasing or decreasing them. The relatively lower pituitary--adrenal activation when a single partner was present also indicated that the social environment can affect an individual's general level of arousal and subsequently alter the response to stressful stimuli.

Animals↗

Predictability, control, and the pituitary-adrenal response in rats.

Five experiments were performed to compare to effects of signaled and unsignaled shock on the pituitary-adrenal response of rats. In Experimental 1, exposure to the two procedures yielded no difference in plasma corticosterone levels. In Experiment 2, the addition of a food-reinforced lever-pressing baseline produced conditioned suppression in the signaled condition but bo group difference in steroid values. In Experiment 3, in order to guard against steroid elevations produced by exposure to shock per se, blood samples were obtained during brief test sessions prior to the occurrence of shock. The procedure resulted in a significant elevation in the steroid levels of the signaled shock group. In Experiment 4, a within-subjects sampling procedure revealed that disparate group steroid values obtained earlier in the session had converged by the end of the test session. The final experiment replicated the original failure to obtain a steroid difference due to predictability in the absence of a behavioral baseline, despite the fact that blood samples were obtained by using the early "probe" sampling procedure. Collectively, these results suggest that (a) the effects of predictability are largely seen in the temporal pattern of steroid elevation and not in their terminal values, (b) the effects of predictability on steroids are modulated by the availability of control, and (c) control is not confined to the stimulus that is being predicted.

Animals↗

Adrenocortical response to hypertonic saline in rats with lateral hypothalamic lesions.

Plasma corticosterone levels were used to assess the response to stress induced by intraperitoneal injections of hypertonic saline in rats with lateral hypothalamic (LH) or sham lesions. Rats with LH lesions displayed a corticosterone response equal to that of normal animals under basal conditions, after control injections of isotonic saline, and 20 min after injection of hypertonic saline (1.5 M, 1.0 ml/100 g of body weight). The corticosterone response of animals with LH lesions, however, was significantly less than that of normal animals 90 min after injection of hypertonic saline when no water was available. With access to water, normal animals displayed substantial drinking (14.5 ml/90 min), which resulted in a reduction in plasma corticosterone concentrations to a level observed after a control injection of isotonic saline, but the little water ingested by animals with LH lesions (2.5 ml) had no effect on the pituitary-adrenal system. It is concluded that the failure of animals with LH lesions to drink following a hydrational challenge is not the result of an exaggerated response to stress.

Adrenal Cortex↗

Hypothalamic and medullary lesions caused by an aliphatic triamine unrelated to goldthioglucose.

A single subcutaneous injection of 3.3'-methyliminobis-(N-methylpropylamine) caused edema and necrosis in the hypothalamus and medulla oblongata of rats, mice, and gerbils. Most other aliphatic triamines were ineffective. The lesions were very similar in character and distribution to those caused by goldthioglucose or bipiperidyl mustard. When compared to closely-related analogs, the biological activity of each of these three compounds is determined by a highly specific chemical structure, yet they have no structural similarities to each other. These data cast doubt on the theory that goldthioglucose causes lesions and, eventually, obesity by binding to a hypothalamic glucoreceptor. Alternatively, the localization of brain damage in hypothalamus and medulla has been attributed to proximity to median eminence and area postrema, and to the lack of a blood-brain barrier in the latter structures. This theory is supported by our finding that artificial disruption of blood-brain barrier in the cerebral cortex induced the localization of necrosis from the triamine in that area. Furthermore, these experiments provide evidence for the role of ischemia in the development of necrotic triamine-induced lesions.

Animals↗

Further studies on the inflammatory response induced by zinc wire implants in the central nervous system of rats.

Implantation of zinc wires into the central nervous system of adult Lewis rats initiates an inflammatory reaction with a predominantly mononuclear cell profile. Extensive cuffs of small lymphocytes, mature plasma cells, macrophages, and histiocytes are found around the site of the wire implant and around adjacent blood vessels. The inflammatory response persists for at least 35 weeks but, with time , is gradually replaced by extensive fibrosis, collagen deposition, and proliferation of glial cells in the adjacent neuropil. The Lesion is not necrotic, nor is it characteristic of a foreign body granuloma, since neither giant cells nor organized epithelioid cells are found. No obvious clinical effect is observed. The fact that the implantation of zinc wire initiates an inflammatory response which resembles certain immune-mediated reactions is consistent with the reports of others that zinc affects immunological responses both in vivo and in vitro. Other metals (Be, Co, Mg, Pt, and Ni), implanted to control for the effect of zinc, initiated responses that were both distinct for the metal used and reproducible, and thus underscore the significance of studying the role of metals in both acute and chronic diseases.

Animals↗

Ultrastructure of hypothalamic and medullary lesions caused by an aliphatic triamine.

The administration of an aliphatic triamine, 3,3'-methylimino-bis-(N-methylpropylamine), was used to produce non-necrotizing lesions in the hypothalamus and medulla oblongata of rats. The distribution of the lesions in the hypothalamus was similar to that produced by goldthioglucose, and consisted ultrastructurally of marked distention and edema of the extracellular space, with no confined to the dorsal aspect, in the region of the area postrema. The data suggest that the absence of blood-brain barrier in these sites plays a role in the production of lesions, at least in the initial stages, as has been proposed for goldthioglucose lesions.

Animals↗

Effects of respiratory gases on the frequency and duration of obstructive apneic episodes in a patient with the sleep apnea-hypersomnolence syndrome.

We studied the effects of hyperoxia and hypercapnia on obstructive apneic episodes (OAE) in a 39-year-old male with the sleep apnea and hypersomnolence syndrome (SAHS). While inspiring room air, our patient spent approximately 50% of his non-REM sleep time in OAE. When the inspired gas was changed to 100% oxygen, the frequency of the OAE decreased slightly, but a statistically significant increase in the duration of each episode was noted. Additionally, a CO2 rebreathe under hyperoxic conditions was carried out during non-REM sleep; no OAE were noted during this rebreathe. Therefore, this latter observation suggests that hypercapnia under hyperoxic conditions may reduce the frequency of OAE in patients with the SAHS.

Adult↗

Localization of toxic encephalopathies near lesions of experimental allergic encephalomyelitis.

Bipiperidyl mustard and a neurotoxic triamine are known to cause edematous and/or necrotizing lesions in particular areas of hypothalamus and dorsal medulla but not in spinal cord. Experimental allergic encephalomyelitis (EAR) causes widespread inflammatory lesions that are especially numerous in spinal cord. When the chemical toxicants were administered to rats during the acute phase of EAE, mortality was increased. This was due to a specific interaction between EAE and chemical toxicants leading to the development of necrotizing vasculitis and parenchymal necrosis near EAE lesions in spinal cord or brain. The interaction decreased as the EAE lesions healed. Another neurotoxic chemical, dipiperidinoethane, did not produce this phenomenon. These effects of EAE are probably related to damage to the vessel walls and the blood-brain barrier. The present work may increase the versatility of EAE as a model for multiple sclerosis if the EAE lesions can be enlarged progressively by repeated exposures to the toxicant.

Animals↗

Effects of zinc on the cytoskeletal proteins in the central nervous system of the rat.

To test for in vivo zinc neurotoxicity on the cytoskeleton of neurotubules and intermediate filaments, Zn wires were implanted into the brains of adult Lewis rats for periods of 1-35 weeks. After 16 weeks of implant, some neurons showed bundles of intermediate filaments which were often localized in the perinuclear area. At the same time, occasional 200 nm tubular-like structures were seen in swollen dendrites. These structures were morphologically similar to Zn ion-induced aggregates of pure tubulin and structures found in ZnSO4-treated dorsal root ganglion organotypic cultures. The 200 nm structures in dendrites and the intermediate filaments in neurons increased in frequency with time. After 35 weeks of Zn wire implant, few microtubules could be found in the lesion. All the animals showed an astrocyte and glial filament proliferation with axoglial membrane specialization. Other wires studied: Pt, Ni, Co, Mg, demonstrate that Zn wires have a specific effect on cytoskeletal proteins in the CNS of the rat and many of the effects can be explained by an interaction between Zn and tubulin.

Animals↗

Tyrosine hydroxylase activity in Venezuelan equine encephalomyelitis virus infection.

In rats inoculated with the Venezuelan equine encephalomyelitis (VEE) virus, a significant decrease was found in the tyrosine hydroxylase activity of neostriatum, midbrain, and hypothalamus during the acute phase of the infection. In animals that survived the acute infection, we observed no changes in the enzymatic activity in the same regions studied. Our findings suggest a vulnerability of the dopaminergic and noradrenergic pathways to the infection produced by VEE virus.

Animals↗