Vasopressin Prolongs Behavioral and Cardiac Responses to Mild Stress in Young But Not in Aged Rats

In young male Wistar rats sudden silence superimposed on low intensity background noise evokes a relative decrease in heart rate. This bradycardia is accompanied by immobility behavior. In the present study, involving young (3 month), late-adult (14 month), aged (20 month), and senescent (25 month) rats the magnitude of the stress-induced bradycardia shows an age-related reduction while the behavioral immobility response remained unchanged during the process of aging. Arginine-8-vasopressin (AVP, 6 µg/kg SC) administered 60 min prior to the experiment led to a prolonged behavioral and cardiac stress response in young and late-adult rats, but not in aged and senescent animals. The peripheral and central mechanisms possibly involved in the failure of systemically applied AVP to improve bradycardiac stress responses in aged rats are discussed.

Reduced preabsorptive insulin response in aged rats:differential effects of amphetamine and arginine-vasopressin

The experiments presented here have been designed to investigate whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studied the vagal control of the endocrine pancreas during food intake. Young (3 months old) and aged (27 months old) male Wistar rats were provided with permanent cardiac catheters allowing free movement and repeated, stress-free blood sampling. The vagally mediated preabsorptive insulin response (PIR) in relation to food intake as seen in young rats was reduced in aged ones. Blood glucose increments were the same at both ages. Administration of Amph (0.5 mg/kg; s.c.) 30 min before, or AVP (10 µg/kg; s.c.) 60 min before presentation of a test meal led to an elevation of the magnitude of insulin secretion in young rats but reduced the response in aged rats. Moreover, the PIR was not reinstated in aged rats. Blood glucose increments were not influenced by the treatments. The results are interpreted in terms of age-related general reduction of parasympathetic reactivity. The differential effect of amphetamine and AVP treatment on the insulin response suggests that the central aminergic or peptidergic drive of vagal output to the endocrine pancreas is also age-related

Behavioral and Cardiac Responses to Mild Stress in Young and Aged Rats:Effects of Amphetamine and Vasopressin

Young (3-month-old) male Wistar rats showed a relative decrease in heart rate to a sudden silence superimposed on low intensity background noise. This bradycardia was accompanied by immobility behavior. In 26-month-old rats the magnitude of the heart rate response was reduced while immobility behavior remained in the same order of magnitude as in young controls, in the aged rats a shift in autonomic regulation of heart rate in the direction of increased sympathetic influence was indicated by the results obtained by blocking the autonomic input with atropine methyl-nitrate (0.5 mg/kg) or atenolol (1 mg/kg) given subcutaneously (SC) 30 min prior to testing. Pretest (30 min) administration of amphetamine (0.5 mg/kg SC) reinstated the bradycardiac response in aged rats to a level seen in young ones. Arginine-vasopressin (AVP, 10 µg/kg SC), administered 60 rain before the experiment, markedly facilitated the cardiac response in young animals but failed to restore cardiac responses in aged ones. The immobility behavior in the peptide-treated aged rats was also absent. The present findings suggest that a diminished central aminergic drive in aged rats is causing a reduction of the parasympathetic cardiac response to stress of sudden silence. The results also indicate an age-related vasopressinergic modulation of behavioral and cardiac responses to mild stress

Socially defeated male rats display a blunted adrenocortical response to a low dose of 8-OH-DPAT

The study examined in male Wistar rats the influence of social defeat on the neuroendocrine stress response system using injection of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), as the pharmacological challenge. Social defeat was defined by the submissive postures displayed by the Wistar rats which were threatened and attacked by Tryon Maze Dull S3 rats for 10 min. 18-20 h after social defeat, the defeated rats were injected intravenously (i.v.) with a low and high dose of 8-OH-DPAT in their home cages. Blood samples were withdrawn from the freely moving cannulated rats for determination of plasma corticosterone and catecholamines. The corticosterone response to the low dose of 8-OH-DPAT (0.05 mg/kg, i.v.) was significantly diminished in the defeated rats as compared to the controls, but this dose failed to affect catecholamine concentrations. The high dose of 8-OH-DPAT (0.15 mg/kg, i.v.) significantly elevated corticosterone and adrenaline levels in defeated and control rats to the same extent, whereas no effect on noradrenaline was found. The present data thus indicate that social defeat blunts 5-HT1A receptor-mediated adrenocortical activation probably via a decrease in the sensitivity of a population of postsynaptic 5-HT receptors

Experiments testing seismographic methods for determining crustal structure

This paper sets forth the results of experiments executed with a view to ascertaining the effectiveness of seismographic methods in the determination of the structure of both the more superficial and the deeper parts of the earth's crust

Overfeeding, Autonomic Regulation and Metabolic Consequences

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The overfeeding-induced changes in autonomic outflow occur with typical symptoms such as adiposity and hyperinsulinemia. There might be a causal relationship between autonomic disturbances and the consequences of overfeeding and obesity. Therefore studies were designed to investigate autonomic functioning in experimentally and genetically hyperphagic rats. Special emphasis was given to the processes that are involved in the regulation of peripheral energy substrate homeostasis. The data revealed that overfeeding is accompanied by increased parasympathetic outflow. Typical indices of vagal activity (such as the cephalic insulin release during food ingestion) were increased in all our rat models for hyperphagia. Overfeeding was also accompanied by increased sympathetic tone, reflected by enhanced baseline plasma norepinephrine (NE) levels in both VMH-lesioned animals and rats rendered obese by hyperalimentation. Plasma levels of NE during exercise were, however, reduced in these two groups of animals. This diminished increase in the exercise-induced NE outflow could be normalized by prior food deprivation. It was concluded from these experiments that overfeeding is associated with increased parasympathetic and sympathetic tone. In models for hyperphagia that display a continuously elevated nutrient intake such as the VMH-lesioned and the overfed rat, this increased sympathetic tone was accompanied by a diminished NE response to exercise. This attenuated outflow of NE was directly related to the size of the fat reserves, indicating that the feedback mechanism from the periphery to the central nervous system is altered in the overfed state.

Conditioned neuroendocrine and cardiovascular stress responsiveness accompanying behavioral passivity and activity in aged and in young rats

Mean arterial pressure (MAP), heart rate (HR), plasma epinephrine (E), plasma norepinephrine (NE), and plasma corticosterone (CORT) were measured in 3-month- and 24-month-old male Wistar rats exposed to a conditioned emotional stress response (CER) paradigm and a conditioned defensive burying (CDB) paradigm. In the CER situation blood samples were taken during reexposure to the training environment one day after a single inescapable footshock (0.6 mA, AC for 3 s) had been administered. In the CER paradigm the young rats displayed passive behavior (immobility) accompanied by an increase in plasma levels of CORT and E. whereas both the control and conditioned animals showed increased NE responses. Previously shocked aged rats exhibited an attenuated plasma NE response, whereas levels of E remained elevated to a greater extent. Aged animals showed elevated basal levels of CORT one day after footshock administration. Stress-induced immobility was preserved in the aged rats. These animals had an increase in basal MAP values and a decrease in basal HR values compared to young ones.In the CDB paradigm, rats were exposed to a nonelectrified probe 1 day after the repeated shock (2 mA/contact) procedure. Young rats displayed defensive burying accompanied by increments in MAP, HR, CORT. and NE. The aged animals showed similar hormonal, autonomic, and behavioral stress responses.Thus, the age-related alterations in neuroendocrine and autonomic response patterns are apparent in stressed animals during behavioral passivity in absence of control (CER) rather than during active control (defensive burying).</p

Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis

Background: Tamoxifen (TAM) is an important cancer therapeutic and an experimental tool for effecting genetic recombination using the inducible Cre-Lox technique. Despite its widespread use in the clinic and laboratory, we know little about its effects on the nervous system. This is of significant concern because TAM, via unknown mechanisms, induces cognitive impairment in humans. A hallmark of cellular stress is induction of Activating Transcription Factor 3 (Atf3), and so to determine whether TAM induces cellular stress in the adult nervous system, we generated a knock-in mouse in which Atf3 promoter activity drives transcription of TAM-dependent Cre recombinase (Cre-ERT2); when crossed with tdtomato reporter mice, Atf3 induction results in robust and permanent genetic labeling of cells in which it is up-regulated even transiently. Results: We found that granular neurons of the olfactory bulb and dentate gyrus, vascular cells and ependymal cells throughout the brain, and peripheral sensory neurons expressed tdtomato in response to TAM treatment. We also show that TAM induced Atf3 up-regulation through inhibition of cholesterol epoxide hydrolase (ChEH): reporter expression was mitigated by delivery in vitamin E-rich wheat germ oil (vitamin E depletes ChEH substrates), and was partially mimicked by a ChEH-specific inhibitor. Conclusions: This work demonstrates that TAM stresses cells of the adult central and peripheral nervous systems and highlights concerns about clinical and experimental use of TAM. We propose TAM administration in vitamin E-rich vehicles such as wheat germ oil as a simple remedy