Sympathetic-adrenal Medullary System Research Articles

110. Beta-Adrenergic sensitivity and somatic symptoms of depression in heart failure patients

Background: Depression is prevalent in heart failure (HF) and is considered a powerful predictor of rehospitalization and mortality. Dysregulated sympathetic activity associated with depression may be one pathway. We investigated the relationship between depressive symptoms and alterations in leukocyte beta-adrenergic sensitivity in response to an acute exercise task in HF-patients. Methods: NYHA II–III HF-patients ( n = 13) were assessed for symptoms of depression using the Beck’s Depression Inventory (BDI), sub-categorized into somatic (BDI-s) and cognitive (BDI-c) symptoms. Participants underwent a 15 min bicycle ergometry task using a modified Bruce protocol. Beta-adrenergic receptor sensitivity was measured by quantifying leukocyte cyclic-AMP levels pre- and post-isoproterenol stimulation. Repeated measures analysis-of-variance (MANOVA) was used to measure changes in beta- adrenergic sensitivity in relation depressive symptoms. Results: There was a significant time effect ( p = .006) with increases in stimulated cAMP levels in response to exercise in the HF-patients. Moreover,there was a time x-somatic symptoms interactions ( p = .016) for stimulated cAMP. Although HF-patients with elevated somatic symptoms of depression appeared to have elevated basal stimulated cAMP levels, they responded less to the exercise task then those with low somatic symptoms of depression. Conclusions: HF-patients with low BDI-s had an increase in beta-receptor sensitivity due to exercise. However in HF-patients with high BDI-s, elevated basal and reduced stimulated cAMP level response to exercise suggest sympathetic dysregulation. This is consistent with the hypothesis that depression is related to over-activation of the sympathetic–adrenal–medullary system, causing dysregulation of beta-adrenergic activity. Further study is needed to identify clinical implications and HF-disease prognosis.

Sex-Specific Dissociations in Autonomic and HPA Responses to Stress and Cues in Alcohol-Dependent Patients with Cocaine Abuse

Chronic alcohol and drug dependence leads to neuroadaptations in hypothalamic-pituitary-adrenal (HPA) and sympathetic adrenal medullary (SAM) stress systems, which impact response sensitivity to stress and alcohol cue and facilitates risk of relapse. To date, gender variations in these systems have not been fully assessed in abstinent alcohol-dependent individuals who also met criteria for cocaine abuse. Forty-two (21 M/21 F) early abstinent treatment-seeking substance-abusing (SA) men and women and 42 (21 M/21 F) healthy control (HC) volunteers were exposed to three 5-min guided imagery conditions (stress, alcohol/drug cue, neutral relaxing), presented randomly, one per day across three consecutive days. Alcohol craving and anxiety ratings were obtained as well as measures of heart rate (HR), blood pressure, plasma ACTH, cortisol, norepinephrine (NE) and epinephrine (EPI). SA males showed increased ACTH and EPI basal tone compared with HC males and SA females. However, they demonstrated no increase in ACTH and cortisol levels following stress and alcohol cue imagery exposure compared to the neutral condition. SA females demonstrated a typically increased stress response in both measures. In addition, SA males showed no increase in cardiovascular response to either stress or cue, and no increase in catecholamine response to cue compared with their response to neutral imagery. Again, this dampening was not observed in HC males who produced significantly higher levels of cue-related HR and EPI, and significantly higher stress-related DBP. In contrast, SA females showed an enhanced ACTH and cortisol response to stress and cue compared with neutral imagery and this was not observed in the HC females. They also demonstrated a reduced increase in NE and EPI compared with both SA males and HC females as well as reduced HR compared with HC females. While SA males showed a generalized suppression of HPA, SAM system and cardiovascular markers following both stress and cue, SA women demonstrated a selective sympatho-adrenal suppression to stress only and an enhanced HPA response to both stress and cue. These gender variations are discussed in terms of their potential impact on relapse vulnerability and treatment outcome.

Adrenoceptors and Adaptive Mechanisms in the Heart during Stress

Several cardiovascular disorders have been related to alterations in beta-adrenoceptor (beta-AR) signaling at or beyond the receptor level. During the stress reaction, the sympathetic-adrenal medullary system and the hypothalamus-pituitary-adrenal cortex axis are activated, causing beta-AR overstimulation and remodeling of the beta(1)/beta(2)/beta(3)-AR ratio in cardiomyocytes. In a model of foot-shock stress, we described decreased beta(1)-AR signaling occurring simultaneously with increased beta(2)-AR signaling, whereas the response to the nonconventional agonist, CGP12177, was not altered. These alterations may play an adaptive role to the increased sympathetic drive to the heart, protecting the cardiac tissue from the cardiotoxic effects mediated by beta(1)-ARs overstimulation without altering cardiac output, since this would be sustained by the beta(2)-AR, which would also protect myocytes from apoptosis. Moreover, the selective enhancement of the beta(2)-AR population might help to diminish the risk of overstimulation since this adrenoceptor subtype couples to both, stimulatory G (Gs) and inhibitory G (Gi) proteins. On the other hand, in the model of neurogenic hypertension, the decrease in beta(1)-AR-mediated response is not followed by increase in the beta(2)-AR-mediated response. However, the response to CGP12177, which was desensitized 48 h after the surgery, was normalized 7 days after that, when beta(1)-AR were downregulated. Therefore, both experimental models provided evidence that the classical isoform of beta(1)-AR and the recently described low-affinity isoform of beta(1)-AR show independent behavior and provide the heart with adaptive mechanisms to increased sympathetic stimulation during stress.

Workplace observation of work stressors, catecholamines and musculoskeletal pain among male employees

Prolonged activation of the sympathetic-adrenal medullary system during work and the lack of recovery after work may indicate a risk for musculoskeletal pain (ie, neck, shoulder, or low-back pain). This field study tested whether a high level of work stressors are associated with musculoskeletal pain and higher urinary norepinephrine excretion rates at work, after work, and on Sundays. Altogether 32 male employees working in adult education took part in a three-phase repeated-measures field study including workplace observation, self-report of musculoskeletal pain, and measurement of urinary catecholamine at work, in the evening after work, and at corresponding times on Sundays. In univariate analyses, work stressors and workday levels of norepinephrine were significantly higher in the participants with high levels of musculoskeletal pain. Moreover, regressing workday norepinephrine excretion rates on predictor variables in the multilevel regression analysis showed a significant interaction between work stressors and musculoskeletal pain (P=0.011) with elevated excretion rates of norepinephrine in those exposed to a high level of work stressors and, at the same time, reporting higher levels of musculoskeletal pain. High work stressors turned out to be associated with musculoskeletal pain and norepinephrine concentration in male employees. Increased activity of the sympathetic-adrenal medullary system seems to play an important role in work-related musculoskeletal pain.

Neuroendocrine profiling in inherited stress-induced arterial hypertension rat strain with stress-sensitive arterial hypertension

The functions of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems were studied in rats with inherited stress-induced arterial hypertension (ISIAH strain). A characteristic feature of the ISIAH strain is an increase in arterial blood pressure measured both under basal conditions and after restraint stress in particular. In the control ISIAH rats, the basal plasma ACTH concentration was slightly lower than that in the normotensive Wistar albino Glaxo (WAG) rats, and no differences were found in plasma corticosterone. However, the 0.5-h restraint stress produced higher activation of the adrenal cortex in the ISIAH rats. Gluco- and mineralocorticoid responses to the blood volume reduction stresses and ACTH and corticosterone responses to social stress were stronger in the ISIAH than in the control WAG rats. An increase in epinephrine content in adrenals in the basal state and enhanced response of the sympathetic adrenal medullary system to handling stress were observed in the ISIAH rats. Restraint stress produced significantly higher expression of genes encoding corticotropin-releasing hormone-mRNA in hypothalamus and proopiomelanocortin-mRNA in pituitary in the ISIAH than in the WAG rats. Restraint stress produced a decrease in glucocorticoid receptor (GR) gene expression (GR-mRNA) in hippocampus in the ISIAH, but not in the WAG rats. A persistent increase in tyrosine hydroxylase-mRNA in adrenals of the ISIAH rats was found. It is concluded that the ISIAH rat strain is an appropriate model of stress-sensitive hypertension with the predominant involvement of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems in its pathogenesis.

Behavioral and Physiological Responses of Trap-Induced Stress in European Badgers

Reasons for mammal trapping include removal of individuals for population management purposes, scientific purposes, pest control, and obtaining fur, skin, or meat for economic purposes. The type of trap used highly affects the responses of captured animals (Kreeger et al. 1990a, White et al. 1991). Research on captured red foxes (Vulpes vulpes) has shown that foothold traps inflict greater trauma compared with box traps even when the traps had padded jaws (i.e., the animal does not experience any obvious physical damage, Kreeger et al. 1990a). Also procedures, such as chemical immobilization, have been shown to affect the life history of mountain goats (Oreamnos americanus; Cote et al. 1998), moose (Alces alces; Ballard and Tobey 1981), and polar bears (Ursus maritimus; Ramsay and Stirling 1986). Thus, not only can entrapment cause physical trauma, such as limb, tissue, or tooth damage, but the overall response is likely to be affected by how the animal perceives the situation. White et al. (1991) demonstrated higher pathological responses in red foxes captured in box traps compared with untrapped individuals, which shows that even traps like box or cage traps that are likely to minimize physical injuries can have negative effects on animals. Stress-induced hyperthermia has been shown to be closely associated with activation of the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenalmedullary system, for example, in foxes (Moe 1996), thus, resulting in increased heart rate, body temperature, and cortisol levels. Cortisol levels have been used as indicators of stress during restraint of wildlife species (Morton et al. 1995), but although physiological responses often can be useful indicators of stress (Broom and Johnson 1993), it is not suitable to use them alone as stress indicators (Rushen 1991) because similar reactions can also be observed during nonstress situations (Kreeger et al. 1989, 1990b). It is well-known that psychological factors may cause or increase stress responses in animals. If an individual is in a threatening environment and is not able to cope with the situation it is likely to be stressed even without any physical injury (Jensen and Toates 1993, Toates 1995, Jensen 1996). An animal’s ability to predict or control its situation highly influences the response, with stress levels decreasing with increased ability to predict or control the situation (Weiss 1972, Jensen 1996). Therefore, besides potential physical trauma, a captured animal might also be exposed to psychological stress by experiencing lack of control because it is unable to escape from the trap. Furthermore, during long entrapment times there is also a risk of enhanced stress levels due to disruption of, or failure to perform, natural behaviors such as feeding. External factors, such as type of trap, entrapment duration, and time of day, most likely affect the stress response. Also species-specific factors, such as diurnal rhythms, general activity levels, and sociality, are likely to have an influence on how the animal responds to the situation. The European badger (Meles meles) is a nocturnal species that lives in social groups varying in size from 2–30 individuals (Rogers et al. 1997). A group uses a shared territory with one or several setts, but the individuals commonly feed independently from each other (Kruuk 1978a). Badgers are used in Sweden to train earth dogs (i.e., dogs that enter the sett when hunting [e.g., foxes and badgers]), and our study was a part of a project investigating stress coping in such badgers on commission of the Swedish Ministry of Agriculture, Food, and Consumer Affairs. Our aim was to examine some behavioral and physiological (heart rate, body temperature, and fecal cortisol) responses of semitame European badgers to restraint in cage traps for short and long capture periods during day and night time. We also studied behavior during 3 consecutive nights postrestraint (i.e., after the treatment period) and compared behavior to undisturbed conditions. We predicted that longer entrapment would affect the badgers more than short entrapment periods in terms of higher heart rate, body temperature, and fecal cortisol metabolites (FCM) levels and in terms of more long-term changes in behavior. We also predicted that entrapment during dark hours when badgers normally are active would be more stressful than during daylight.

Type 2 Diabetes and its Association with Hypertension and Depression in an Iraqi Population

The association of type 2 diabetes mellitus and hypertension is so high that it cannot be explained on the basis of diabetic nephropathy. This phenomenon has been attributed to a condition known as metabolic syndrome. Depression may be another aspect of metabolic syndrome. We conducted a cross-control study with 110 patients with type 2 diabetes mellitus (DM) and 110 control subjects of comparable age and sex. We determined the time since diagnosis of diabetes, the presence of hypertension (HT), coronary heart disease, cerebrovascular insufficiency, and depression, and took several anthropometric measurements, including height, weight, body mass index (BMI) waist circumference (WC), waist-to-hip circumference ratio (WHR), triceps skin fold thickness (TSFT), mid-upper arm circumference (MUAC), and mid-upper arm muscle area (MAMA). We also investigated depression in metabolic syndrome by comparing patients with type 2 diabetes alone and with type 2 diabetes and hypertension who attended a diabetes clinic. The prevalence of depression in hypertensive diabetics was 57% whereas in diabetics alone it was 40% (X2=4.3, P is less than 0.05). Likewise, combined hypertension and depression was more common among diabetics than controls (66% vs 25% respectively P is less than 0.01). The presence of combined hypertension and type 2 diabetes should alert the clinician to look for other features of the metabolic syndrome and for associated depression, which should be treated in most cases by pharmacotherapy.

The dissociation of catecholamine and hypothalamic-pituitary-adrenal responses to daily stressors using dexamethasone.

The hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) systems are implicated in the human stress response. One characterization of these systems is that they are nonspecific in their response, but differ in activation threshold and time course. Additionally, they have been found to be affected commonly by strong metabolic stressors and infusions of CRH, and a hypothesis has been developed primarily from animal research that CRH stimulates both the HPA and SAM systems. To determine whether CRH was significantly involved in tonic as well as psychological stress-induced catecholamine levels in man, we infused 24 normal male undergraduate students with either saline (n = 12) or dexamethasone (DEX; n = 12) and evaluated their subsequent plasma levels of ACTH, cortisol, epinephrine (EPI), and not epinephrine (NEPI). DEX produced a dramatic decrease in ACTH and cortisol levels, but no significant changes in EPI or NEPI occurred over a 4-h sampling interval. After the administration of math and speech stressors in a controlled laboratory setting, DEX inhibited the ACTH and cortisol release that was noted in the saline group, but stress-induced increases in EPI and NEPI were comparable in both groups. Thus, our study suggests that there is a difference in the neural pathways for tonic and stress-induced stimulation of the SAM and HPA systems.

Regulation of plasma catecholamine responses to stress

Plasma levels of norepinephrine and epinephrine provide an accurate assessment of the functional state of the sympathetic-adrenal medullary system. In laboratory rats, plasma levels of both catecholamines increase monotonically with increases in stressor intensity. In addition, plasma catecholamine responses are reduced in animals exposed repeatedly to the same stressor (habituation). In contrast, plasma catecholamine responses increase significantly when animals are exposed repeatedly to an intense stressor (sensitization). Finally, plasma catecholamine responses are increased markedly when previously stressed animals are exposed to a novel stressor (dishabituation). Nonassociative processes appear to underlie the adaptive responses of the sympathetic-adrenal medullary system in animals exposed to chronic intermittent stress.

Maternal influences on sympathetic-adrenal medullary system in spontaneously hypertensive rats

The technique of reciprocal cross fostering was used to assess the influence of the maternal environment on the functioning of the sympathetic-adrenal medullary system in the spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive rats. Control, in-fostered, and cross-fostered rats were tested in adulthood to assess 1) the neural contribution to resting mean arterial blood pressure (MAP) and 2) sympathetic-adrenal medullary responses to acute footshock stress. Adult resting MAP was significantly lower in cross-fostered SHRs (139.6 mmHg) compared with control or in-fostered SHRs (162.1 and 159.3 mmHg). In addition, the decrease in MAP after sympathetic blockade (40.6 mmHg) was significantly less in cross-fostered SHRs compared with controls (50.1 mmHg). Sympathetic-adrenal medullary responses to foot-shock were greater in SHR than WKY rats; however, cross-fostered SHRs showed exaggerated responses compared with control and in-fostered SHRs. Altering the maternal environment did not produce any measurable effects on the neural contribution to resting MAP or sympathetic-adrenal medullary responsivity to acute stress in the WKY strain. These results indicate that the blood pressure-lowering effect of cross fostering in the SHR strain is caused in part by a dampening of the neural contribution to resting MAP; however, these animals retain their strain's characteristic adrenergic hyperreactivity to stressful stimulation.

Habituation of plasma catecholamine responses to chronic intermittent restraint stress

Adult male Sprague-Dawley rats were exposed to restraint stress (RS) for 30 min per day for 0, 5, 12, or 26 consecutive days. Each animal was then surgically prepared with an indwelling tail-artery catheter to permit direct measurements of mean arterial pressure (MAP, in mm Hg) and heart rate (HR, in beats per minute) on the day after surgery, and remote collection of blood samples during RS 2 days after surgery. Blood samples were later analyzed for plasma levels of norepinephrine and epinephrine to provide an assessment of the activity of the sympathetic-adrenal medullary system. Body-weight gain was reduced significantly in rats stressed for 12 or 26 days relative to handled controls. Baseline values of HR and of plasma levels of norepinephrine and epinephrine were similar in animals of the four groups. Baseline MAPs were lower in control rats and in those stressed for 26 days than in rats stressed for the previous 5 or 12 days. Plasma catecholamine responses to RS were reduced significantly in animals during the 6th, 13th, or 27th stress session relative to subjects restrained for the first time. These findings indicate that sympathetic-adrenal medullary responses are dampened rapidly when laboratory rats are exposed to chronic intermittent RS. In addition, the results of this experiment are consistent with our suggestion that habituation of sympathetic-adrenal medullary responsiveness occurs in animals exposed to chronic intermittent stress.

Hormonal and metabolic responses of untrained, moderately trained, and highly trained men to three exercise intensities

Untrained, moderately trained (runners, 15 to 25 mi/wk), and highly trained (runners, >45 mi/wk) men participated in graded treadmill exercise at 50%, 70%, and 90% of their maximal oxygen consumption to quantify the relation between intensity of exercise and sympathetic nervous system and metabolic responses. Sympathetic system activation was noted at all intensities tested and was proportional to the relative exercise intensity. The magnitudes of the norepinephrine (NE) and epinephrine (E) responses were similar in all three groups of men at each relative exercise intensity and correlated with the magnitudes of change in levels of circulating plasma adrenocorticotropin hormone, cortisol, lactate (La), phosphate (Pi), and glucose (Gl). The magnitudes of change in concentrations of La, Pi, and Gl were also similar for the three groups at each relative exercise intensity. In contrast, a lower degree of sympathetic system activation in response to a given absolute workload was noted in the moderately and highly trained men as compared to that of the untrained men. Sympathetic and metabolic responses to exercise are similar under conditions of comparable relative exercise intensities, regardless of conditioning level. The sympathetic-adrenal medullary system is more sensitive to exercise than the hypothalamic-pituitary-adrenal axis. For a given absolute workload, the degree of activation is significantly lower in trained individuals.

Chronic stress and sympathetic-adrenal medullary responsiveness

Acute exposure of animals to stressful stimulation is attended by a significant activation of the sympathetic-adrenal medullary system. If animals are exposed to the same stressful stimulus each day for several weeks, a number of adaptive changes occur in the sympathetic-adrenal medullary system, including increased synthesis and storage of catecholamines, increased basal levels of circulating catecholamines, and decreased release of catecholamines into the circulation following exposure to the identical (homotypic) stressful stimulus. If chronically stressed animals are exposed to a novel (heterotypic) stressful stimulus, there is an exaggerated response of the sympathetic-adrenal medullary system compared to animals exposed to the same stressful stimulus for the first time. Other neuroendocrine systems share some characteristics with the sympathetic-adrenal medullary system in its pattern of adaptation to chronic stress. Several variables appear to influence this pattern of neuroendocrine adaptation to stressful stimulation, including predictability of the stressor, the intensity and duration of the stressor, the interval between each episode of stress, and the number of presentations of the stressor. The pattern of neuroendocrine adaptation to chronic intermittent stressful stimulation resembles in some respects the processes of habituation and sensitization.

Bereavement and catecholamines

Urinary catecholamine output was studied in 59 middle-aged and elderly persons who were either acutely bereaved ( n=39) or threatened with the loss of a spouse ( n=20). The study was done with the hypothesis that urinary catecholamine output would be elevated among the bereaved subjects both in comparison to norms in the literature for non-stressed controls and to the group of subjects who were threatened with a loss. It was also expected that individually high measures of psychological distress would be associated with high urinary catecholamines. Twenty-four hour urinary output of norepinephrine and epinephrine was observed to be higher than normal during acute bereavement but was not associated with depression scores. No differences were found between those who had experienced an actual loss two months earlier and those who were threatened with a loss. Expected relationships between indices of psychological distress and catecholamine output were not observed. Finally, an association was found between increasing age and higher levels of urinary norepinephrine and epinephrine output among acutely bereaved subjects, suggesting that the adaptation of the sympathetic-adrenal medullary system to stress among older persons is slower.

Circadian rhythms of epinephrine and norepinephrine in man.

The diurnal rhythms of plasma epinephrine and norepinephrine were investigated in a group of normal young men. Sleep, posture, illumination, and food intake were monitored. Plasma epinephrine demonstrated a statistically significant diurnal rhythm, with a mean amplitude of 14 +/- 1.6 (+/- SE) pg/ml superimposed on a mean level of 43 +/- 5.3 pg/ml. The trough occurred at 03.20 h +/- 35 min. Plasma norepinephrine had a significant diurnal rhythm, with a mean amplitude of 111 +/- 19 pg/ml superimposed on a mean level of 413 +/- 25 pg/ml, with the trough occurring at 02.20 h +/- 30 min. There was a significant correlation between the two rhythms at zero phase shift, with a pooled value for the group of r = 0.49. Epinephrine levels had no direct relationship to sleep or posture, whereas norepinephrine levels were significantly higher with upright posture and higher when the men were awake than when asleep. Our results indicate that circadian variations in the sympathetic-adrenal medullary system are not explained by a single controlling influence and that the norepinephrine rhythm can be accounted for as a direct response to changes in posture and sleep, whereas the epinephrine rhythm is probably controlled by a circadian oscillator.

Role of emotions and stress in the genesis of sudden death

Emotional arousal induces dramatic endocrine responses through either the sympathetic-adrenal medullary system or pituitary-adrenal cortical system. Many of the known actions of cortisol and catecholamines are atherogenic, cardiotoxic and arrhythmogenic. Emotional stress can produce sudden cardiac death in experimental animals, as can the administration of exogenous catecholamines. Previous studies have found that emotional stress is a common precursor to sudden cardiac death. Thus, acute neuroendocrine arousal, superimposed on a substrate of compromised myocardium and electrical instability, may constitute an important, final inciting event in sudden cardiac death.

Sympathetic-adrenal medullary and cardiovascular responses to acute cold stress in adult and aged rats

In this study, adult (5 months) and aged (22 months) Fischer 344 (F-344) male rats were surgically prepared with chronic tail artery cannulae. Two days after surgery, rats were stressed by immersion in 12°C water for 10 min. Blood samples (0.5 ml) were collected before and at timed intervals after cold immersion (0, 15 and 60 min) and were later assayed for content of norepinephrine and epinephrine. Consistent with earlier studies from this laboratory, there were no differences between ages in basal plasma levels of either catecholamine or in mean arterial pressure or core temperature. However, basal heart rates of aged rats were approximately 10% greater than values for adult rats. During cold immersion, aged rats had greater decrements in heart rate compared to adults but there were no age-related differences in mean arterial pressure or core temperature. Immediately following cold immersion, increments above basal values for plasma norepinephrine and epinephrine (4.2–4.6 and 11.8–14.1-fold, respectively) were similar for 5- and 22-month-old rats. However, in aged rats plasma norepinephrine was greater at 60 min post-immersion and plasma epinephrine was greater at 15 and 60 min post-immersion compared to values for adults. These findings support the following conclusions: (1) basal activity of the sympathetic-adrenal medullary system does not appear to be altered in aged rats, (2) the ultimate peak sympathetic-adrenal medullary response of aged rats to the intense and prolonged stressor used is equivalent to that of adult rats, however, (3) the sympathetic-medullary system of aged rats reacts less quickly but remains more active for a longer period than in normal adults, requiring significantly more time for recovery from an intense and prolonged stressful experience. These age-related alterations in regulation of the sympathetic nervous system may contribute to the reduced survival of aged animals during chronic exposure to stressful stimulation.

Effects of 2-deoxyglucose on plasma catecholamines in adult and aged rats

To examine the effects of aging on the responsiveness of the sympathetic-adrenal medullary system, I have measured plasma levels of norepinephrine (NE) and epinephrine (EPI) in adult (6 months old) and aged (24 months old) Fischer 344 male rats. Two days prior to testing, rats were surgically prepared with chronic tail artery catheters to permit remote sampling of blood in conscious, unrestrained animals. Following collection of basal blood samples, each rat received a single injection of 2-deoxyglucose (2-DG, 250 or 500 mg/kg, IP) and additional blood samples were collected 1, 2 and 4 hours later. 2-DG, a glucose analogue, stimulates a centrally mediated activation of the adrenal medulla and to a lesser extent the postganglionic sympathetic neurons. For purposes of analysis, data were excluded from animals which died within 4 hours after injection. Basal plasma levels of both catecholamines were similar in adult and aged rats. Administration of 2-DG was attended by significant and sustained increases in plasma NE and EPI in rats of both ages. A greater proportion of aged rats died following administration of 2-DG compared to adult rats. At the higher dose of 2-DG, plasma levels of NE were significantly higher in 6 month old rats at 1 and 2 hours post-injection. In contrast, plasma levels of EPI were significantly higher in 24 month old rats at 1 and 2 hours after administration of 250 mg/kg 2-DG and at 1 hour after administration of 500 mg/kg 2-DG. These findings indicated that the adrenal medullary response of aged rats to an intense and prolonged stressor is greater than that of adult rats. The attenuated plasma NE response of aged rats to 2-DG may be due to a lessor release of NE from the adrenal medulla and/or a diminished activation of postganglionic sympathetic nerves.

Influence of shock-induced fighting and social factors on pituitary-adrenal activity, prolactin and catecholamine synthesizing enzymes in rats

The present experiment investigated changes in pituitary-adrenal activity, prolactin and catecholamine synthesizing enzymes in rats exposed to electric shocks in pairs or individually, in comparison to animals receiving no shock and tested in pairs or alone. Pairs of rats repeatedly exposed to electric shocks displayed a lower activation of the pituitary-adrenal system but a stronger activation of the sympathetic-adrenal medullary system than rats shocked individually. There was no differential release of prolactin according to the social setting in which shock occurred. Social factors by themselves influenced plasma corticosterone levels but not plasma levels of ACTH and prolactin nor catecholamine synthesis. These results are discussed in relation to the postulated beneficial effects of fighting on physiological activation produced by electric shock.

Choline administration: Lack of effect on plasma catecholamines in rats

Choline chloride (35 or 70 mg/kg, IP) or saline was administered daily for 3 consecutive days to adult male Sprague-Dawley rats. Before and 30, 60 and 120 minutes after the third injection of choline chloride or saline, blood samples were collected from a chronic tail artery catheter and later analyzed for levels of norepinephrine (NE) and epinephrine (EPI). Plasma levels of both catecholamines did not differ between choline- and saline-injected rats at either of the four sampling points. When insulin (10 IU/kg, SC) was administered to stimulated the sympathetic-adrenal medullary system reflexy, plasma levels of NE and EPI increased significantly above basal values but were similar for choline- and saline-injected rats. These findings do not support a role for choline availability in the regulation of catecholamine secretion from the adrenal medulla.