Effect of vagotomy on plasma levels of growth hormone, free fatty acids and glucose in the pigeon

Plasma levels of growth hormone (GH), free fatty acids (FFA) and glucose were measured in vagotomized (VgX) and sham-operated (VgS) control pigeons. In VgX pigeons, GH level was significantly lower whereas FFA and glucose levels were higher than in VgS pigeons. The depression in GH level in VgX pigeons has been attributed to the significantly high levels of norepinephrine (NE) and corticosterone in these Birds. The higher plasma FFA concentration in VgX pigeons was therefore due to adipokinetic hormonal action other than of GH. It has been suggested that the adrenocorticotrophic hormone (ACTH) and/or NE could have produced the increase in plasma FFA in VgX pigeons. The pronounced hyperglycemia seen in VgX pigeons has been attributed to catecholamine action in the absence of the vagal tone.     

Flight effects on plasma glucose, lactate, catecholamines and corticosterone in homing pigeons

Significant increase in the circulating levels of glucose, lactate, adrenaline (A) and noradrenaline (NA) was observed in homing pigeons after a flight of 48 km, lasting 60-80 min. There was, however, no change in plasma corticosterone concentrations. The increase in lactate has been attributed mainly to the activity of the white glycolytic fibres in the flight muscles. The increase in A and NA indicated increased sympathetic activity. It is suggested that the flight-induced increase in A stimulated the release of glucagon which could account for the increase in plasma glucose. The lack of any increase in plasma corticosterone implied that the birds were not under any serious stress during the flight and that these results represent the normal changes that may be expected in pigeons during a free flight of the specified distance and duration.     

Changes in hypothalamic noradrenaline and 5-hydroxytryptamine levels during the development of warm- and cold-adaptation in the rat

Hypothalamic 5-hydroxytryptamine (5-HT) and noradrenaline (NA) as well as plasma corticosterone levels were studied in male rats after 1, 2, 4 and 6 weeks of exposure to 4--7 or 30--31 degrees C. An increase of the NA concentration and a decrease of the 5-HT level was observed after the first week in both cold and warm environment together with an increase of plasma corticosterone levels in both groups. NA, 5-HT and plasma corticosterone levels returned to normal in cold-exposed animals by the 6th week whereas in warm-acclimated rats NA and corticosterone levels regained their initial values and 5-HT concentrations remained low. Changes by the end of the first week of exposure may result from the thermal stress. The low 5-HT levels of warm-adapted animals at the end of the 6th week were probably secondary to the process of adaptation.     

Effect of corticosterone on noradrenergic nuclei in the pons-medulla and [3H]NA release from terminals in hippocampal slices

The aim of the present study was to investigate possible membrane and genomic effects of corticosterone on the noradrenergic system of the rat brain. Corticosterone effects were studied in vivo by treating rats s.c. with 10 mg/kg corticosterone for 7 or 14 days. In the first two experiments corticosterone significantly decreased th noradrenaline (NA) and dopamine (DA) levels in the pons-medulla, an area which contains the A1-A7 noradrenergic cell groups, while the NA and DA levels in the dorsal hippocampus remained unchanged. In a third experiment where the locus coeruleus (LC) and the A1 and A2 nuclei (A1,A2) were analysed separately, NA levels were unchanged but total MHPG levels and the total MHPG/NA ratio were decreased in the A1,A2 area. Chronic corticosterone treatment (14 days) did not alter the ₂-adrenoceptor-mediated modulation of [³H]NA release from dorsal hippocampal slices. Neither the spontaneous outflow nor the electrically stimulated release of [³H]NA from dorsal hippocampal slices of untreated rats was affected by exposure of the slices to corticosterone (10^–7 M–10^–4 M) in the superfusion buffer. Thus, chronic corticosterone treatment of rats altered the noradrenergic system of the pons-medulla, but did not change the ₂-adrenoceptor-mediated modulation of NA release in the dorsal hippocampus, a major terminal area of the LC neurons. Corticosterone also did not appear to have a direct membrane effect on the NA terminals in the dorsal hippocampus of the rat.     

Regulation of the hypothalamic-pituitary-adrenal axis in free-living pigeons

We studied feral free-living pigeons (Columba livia) to determine whether either unstressed or stress-induced corticosterone release was altered during a prebasic molt. The pigeons were at various stages of molt throughout the study, but corticosterone responses in molting and nonmolting birds did not differ. This was further reflected in equivalent adrenal responses to exogenous adrenocorticotropic hormone (ACTH), suggesting equivalent steroidogenic capacity of adrenal tissues during both physiological states. There was a slight change, however, in pituitary regulation during molt. Whereas exogenous arginine vasotocin (AVT) elevated corticosterone levels in nonmolting birds, during molt an equivalent dose of AVT was ineffective, suggesting that the pituitary is less sensitive to an AVT signal during molt. AVT also appears to be more effective than corticotropin-releasing factor at eliciting ACTH release in pigeons. Overall, these data indicate that pigeons regulate their corticosterone release differently during molt than other avian species studied to date.     

Diurnal Variation of Plasmatic Melatonin,Corticosterone and Variation of General Activity in Pigeons under Light-Dark Cycle and Constant Light

This work analyzed the diurnal variation of general activity and plasmatic levels of melatonin and corticosterone in pigeons submitted to a 12:00:12:00 h light-dark cycle (lights on at 6:00 a.m.) or to constant light. In both conditions pigeons were observed in 5-min sessions at times 03:00, 06:00, 09:00, 12:00, 15:00, 18:00, 21:00 and 24:00 h during two successive days. Behavior was video taped in the home cages for posterior categorization and quantification. Radioimmunoassays were used to evaluate plasmatic levels of melatonin and corticosterone. Blood samples were obtained at the times of behavioral observation. In the light-dark condition the results showed day-night variation of general activity (p < 0.001) and a robust diurnal rhythm of plasmatic melatonin (p < 0.001). Both of these variations as well as the oscillatory secretion of corticosterone disappeared under constant light condition. The parallel changes in general activity and blunting of melatonin rhythm secretion in constant light condition agree with previous evidences that melatonin may regulate behavioral oscillations in the pigeon. The present data are related to the proposition that the timing system in pigeons may involve neuroendocrine relations characterized by interactions between blood born signalization by melatonin and corticosterone.     

Selective noradrenaline depletion markedly alters stress responses in rats

Rats were given FLA-63, followed by R04-1284 0.5 h later to relatively selectively deplete brain NA. After 8 h, some animals were examined for regional brain NA and MHPG-SO4, while some were subjected to 3 h of cold-restraint stress and then examined. All brain regions examined showed significant NA and MHPG reduction. Specific NA depletion markedly exacerbated restraint ulcer formation and plasma corticosterone levels. NA depletion without restraint stress did not induce ulcers or elevate corticosterone. Intact brain NA activity appears to be essential for coping with stress.     

Rate-limiting, diurnal activity of hepatic microsomal cholesterol-7 alpha-hydroxylase in pigeons with high serum cholesterol

Efficiency of regulating serum cholesterol by cholesterol-7 alpha-hydroxylase was studied in pigeon strains hypo-(SR-39) and hypercholesterolemic (SR-37) with respect to dietary cholesterol. Diurnal hydroxylase activity in SR-37 was 10% of that in strain SR-39 adapted to a light-dark cycle and fed a non-cholesterol diet. Acrophase (6 p.m.) activity was 54-fold greater in SR-39 than in SR-37 pigeons. Dietary cholesterol elevated enzyme activity 2.8-fold in SR-37 pigeons. Dietary cholestyramine plus cholesterol increased hydroxylase activity 21-fold in SR-37 and 3-fold in SR-39 strain; yet, activity remained greater in SR-39. Cholestyramine feeding prevented elevated cholesterol levels in both groups. The circadian rhythms of hydroxylase and serum corticosterone were determined. The diurnal activity in SR-37 was 10% of that in SR-39 and acrophase activity was 34-fold greater in SR-39. Hormone levels were comparable. Programmed acrophase was asynchronous between strains. Hydroxylase activity was positively correlated with corticosterone levels and inversely correlated with serum cholesterol. A defect in the up-regulation of cholesterol-7 alpha-hydroxylase is proposed which limits the catabolism of cholesterol in strain SR-37.     

Hypothalamic monoamines in the cold stress during changes in activity of nitric oxide system

Effects of NO-synthase inhibitor N(omega)-nitro-L-arginine (LNA) and donor sodium nitroprusside (SNP) on alteration in body temperature, plasma corticosterone level and hypothalamic monoamines in response to cold exposure, were studied. Drop of the body temperature in cold exposure in rats treated with LNA or SNP was the same as in the control group. Administration of SNP (2 mg/kg i.p.) significantly increased the basal level of corticosterone (CS). Cold exposure elevated CS in all groups of rats. LNA did not markedly alter the hypothalamic noradrenaline (NA) while SNP significantly decreased the NA. Cold exposure resulted in additional decrease of the NA in SNP-treated rats. NA was found to significantly increase within 48 hrs following the cold exposure in the LNA as well as in the SNP groups. SNP significantly increased basal dopamine and DOPAC levels. Cold exposure did not affect hypothalamic dopamine. In the experiments, NO changes of serotonin and 5-hydroxyindoleacetic acid were observed. The findings suggest that antagonistic effects of the NO-synthase inhibitor and NO donor postulated in literature for various kinds of stress do not occur in experiments with cold stress.     

Effect of clorgyline and of alpha-methyl-p-tyrosine on the plasma levels of corticosterone in the rat

The effect of a type A MAO inhibitor, clorgyline, injected alone or with alpha-methyl-p-tyrosine (aMpT) on the plasmatic corticosterone levels estimated at 9 a.m. and 5 p.m. has been studied in male Wistar rats. The clorgyline injected alone produced significant decreases in corticosterone values, especially at 5 p.m., determining a variation lack between the morning and the afternoon levels. When alpha-MpT is associated to IMAO, increases at both points of the day considered in this experiment take place. The amount of NA and 5-HT in the brain was also estimated; clorgyline high increases in Na and 5-HT contents, 5-HT; aMpT reduces the effect of clorgyline, especially as regards content. The results are discussed in relation to this highly specific MAO inhibitor and with the role of these amines as modulators of ACTH secretion. In view of the changes introduced by the aMpT injection, the modifications produced by clorgyline alone are related to NA, but to 5-HT, when the NA synthesis has been interrupted by the tyrosine hydroxylase inhibitor.     

Dopamine-beta-hydroxylase inhibition acutely stimulates rats hypothalamic noradrenaline and dopamine neuronal activity as assessed from metabolic ratios and circulating glucose and ACTH responses

Because central noradrenaline neuronal activity is tonically inhibited by noradrenaline (NA) itself via an action at prejunctional alpha 2-adrenoceptors, it was hypothesised that the blockade of central NA synthesis following acute dopamine-beta -hydroxylase (DBH) inhibition might primarily deplete prejunctional NA levels and result in an increase in central NA neuronal activity through reduced NA autoinhibition. This hypothesis was tested in the rat following the acute administration of the DBH inhibitors diethyldithiocarbamate (DDC) and cysteamine (CSH). Computerised gas chromatography/mass spectrometry was used to precisely measure the hypothalamic levels of NA and dopamine (DA) together with those of their primary neuronal metabolites dihydroxyphenylethyleneglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC), respectively. Both DDC (at 4 h) and CSH (at 30 min.) caused approximately a 50% reduction of hypothalamic NA concentrations. However this was associated with marked and highly significant increases in hypothalamic DHPG levels (by 50-100%) and in the hypothalamic ratio DHPG/NA. Also, when measured after CSH, the hypothalamic levels of the DHPG metabolite 3-methoxy-4-hydroxyphenylethyleneglycol were highly significantly increased. Consistent with increased DA neuronal activity, both DBH inhibitors raised DA and DOPAC levels and also the ratio DOPAC/DA in the hypothalami of treated rats and markedly suppressed serum prolactin levels (all p less than 0.01). The rise in hypothalamic concentrations of DHPG indicates that an increase in hypothalamic NA neuronal activity occurs following DBH inhibition. Significant elevations of blood glucose, corticosterone and ACTH were also observed after DBH inhibition. As we have previously demonstrated that increased central NA activity is associated with elevations of blood glucose, corticosterone and ACTH, these data provide further evidence for a functional increase in central NA activity caused by acute DBH inhibition. It is proposed that the increase in hypothalamic NA activity after DBH inhibition results from a primary depletion of the prejunctional alpha 2-active autoregulatory pool of NA.     

Effects of U-50,488H and U-50,488H withdrawal on catecholaminergic neurons of the rat hypothalamus

Previous report from our laboratory showed that morphine produces a stimulatory effect of hypothalamic noradrenaline (NA) turnover concurrently with enhanced pituitary-adrenal response after its acute injection and during withdrawal. In the present work we have studied the effects of acute and chronic administration of the kappa agonist U-50,488H as well as the influence of U-50,488H withdrawal on the activity of hypothalamic NA and dopamine (DA) neurons and on the activity of hypothalamic-pituitary-adrenal (HPA) axis. A single dose of U-50,488H (15 mg/kg i.p.) significantly increased hypothalamic NA and decreased DA turnover at the time of an enhanced corticosterone release. Rats rendered tolerant to the kappa agonist by administration of U-50,488H twice a day for 4 days showed no changes in corticosterone secretion. Additionally, a decrease in both hypothalamic MHPG (the cerebral NA metabolite) production and NA turnover was observed, whereas DOPAC concentration and DA turnover were enhanced, which indicate the development of tolerance towards the neuronal and endocrine actions of U-50,488H. After naloxone (3 mg/kg s.c.) administration to U-50,488H-tolerant rats, we found neither behavioural signs of physical dependence nor changes in hypothalamic catecholaminergic neurotransmission. In addition, corticosterone secretion was not altered in U-50,488H withdrawn rats. Present data clearly indicate that tolerance develops towards the NA turnover accelerating and DA turnover decreasing effect of U-50,488H. Importantly and by contrast to mu agonists, present results demonstrate that U-50,488H withdrawal produce no changes in hypothalamic catecholamines turnover or in corticosterone release (an index of the hypothalamus-pituitary-adrenal activity), which indicate the absence of neuroendocrine dependence on the kappa agonist. As has been proposed, this would suggest that the mu and the kappa receptor be regulated through different cellular mechanisms, as kappa agonists have a lower proclivity to induce dependence.     

Recovery of stress-induced increases in noradrenaline turnover is delayed in specific brain regions of old rats

Male Wistar rats at 2 and 12 months of age were sacrificed before, immediately following, and at 6 and 24 hours after a 3-hour immobilization stress period. Levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in eight brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant increases of MHPG-SO4 levels in all brain regions examined and significant elevations in plasma corticosterone levels in both 2 and 12 month old rats. In 2 month old rats, the MHPG-SO4 levels in all brain regions returned to control levels within 6 hours after release from the stress. However, in 12 month old rats, the metabolite levels in the hypothalamus, amygdala, pons plus medulla oblongata (pons+med. obl .) and midbrain still remained at significantly increased levels at 6 and 24 hours after the stress. Moreover, in the amygdala of older rats, stress-induced decreases in NA levels persisted even 6 hours after stress. Plasma corticosterone levels also showed significant elevations at 6 and 24 hours after the stress only in 12 month old rats. These results suggest that brain NA metabolism during recovery periods from an acute exposure to a stressful situation is altered by the aging process in such a manner that NA neurons in the hypothalamus, amygdala, pons+med. obl . and midbrain in older rats remain activated by stressful stimuli for prolonged periods of time following release from stress.     

Repercussions of anterior hypothalamic lesions on nycthemeral variations of plasma thyroxine and corticosterone in the pigeon

Plasma thyroxine and corticosterone levels were determined by competitive protein binding assay, at 3 hr intervals, throughout the photoperiod. Pigeons were kept in controlled environment (21 +/- 1 degree C; 14L6-20: 10D). Intact controls exhibited low thyroxine (T4) and corticosterone (B) levels for the light phase of the photoperiod. Values were rising during the night, up to a peak at 03 hr. Electrolytic lesions were placed bilaterally in either the nucleus anterior medialis hypothalami or the n. preopticus, or the n. supraopticus. Circadian rhythms of both T4 and B were markedly altered in all lesioned pigeons, with a shift of very high T4 values to the morning times and a complete disorganization of B patterns, with very heterogeneous values. The possibility is raised that anterior hypothalamic formations participate in the endogenous oscillator circuitry in birds.     

Effect of intraventricular administration of noradrenaline and dopamine on the levels of corticosterone in rats and denervation hypersensitivity resulting from intraventricular administration of 6-hydroxydopamine.

The effects of intraventricular administration of noradrenaline (NA) on the resting levels, stress-induced rises and dexamethasone-induced decreases of plasma corticosterone (B) were studied in rats. The effect of pretreatment with intraventricular administration of 6-hydroxydopamine (6-OHDA) on the effects of NA or dopamine (DA), which was injected intraventricularly, was also examined. The results obtained were as follows: 1) Intraventricular administration of 1.0 μg of NA did not cause a decrease in concentrations of plasma B. 2) Ten μg of NA injected intraventricularly resulted in a rise of the levels of plasma B. 3) The stimulating action of centrally administered NA was more marked when the pre-injection concentrations of B were lower. 4) Pretreatment with intraventricular administration of 6-OHDA facilitated the action of intraventricularly administered NA in the regulation of pituitary-adrenocortical functions. The result suggests a development of denervation hypersensitivity caused by the pretreatment. 5) Intraventricular administration of NA did not block stress-induced rises of plasma B. 6) Intraventricular administration of NA counteracted dexamethasone-induced decrements of plasma B. 7) This counteraction was enhanced by pretreatment with intraventricular administration of 6-OHDA. This also suggests a development of denervation hypersensitivity resulting from intraventricular administration of 6-OHDA. 8) Intraventricular administration of 1.0 μg of DA caused no change in the concentrations of plasma B in either control or 6-OHDA treated animals.     

Naloxene enhances stress-induced increases in noradrenaline turnover in specific brain regions in rats

Male Wistar rats were injected subcutaneously with either saline or naloxone, 1 mg/kg or 5 mg/kg, 10 min before exposure to 1-hour immobilization-stress. Control animals were sacrificed 70 min after respective injections. Levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO₄) in seven discrete brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant elevations of plasma corticosterone which were not affected by pretreatment with naloxone. In the hypothalamus, amygdala and thalamus, immobilization-stress caused significant elevations of MHPG-SO₄ levels, and naloxone at 5 mg/kg significantly enhanced these stress-induced elevations virtually without affecting the basal level of the metabolite. In contrast, in the hippocampus, cerebral cortex and pons plus medulla oblongata, MHPG-SO₄ levels were elevated by stress, but were not affected by naloxone pretreatment. The effect of naloxone on stress-induced reductions of NA levels was unclear, since naloxone by itself (5 mg/kg) significantly decreased the amine levels in 5 of 7 brain regions examined. These results indirectly suggest that endogenous opioid peptides in the hypothalamus, amygdala and thalamus are partly involved in the stress process and attenuate increases in NA turnover induced by stress.     

Effects of electrical stimulation in vivo of M. pectoralis on carbohydrate metabolism with reference to certain liver and blood values in the pigeon

The pectoralis muscles of two groups of anaesthetized pigeons were exercised in vivo by electrical stimulation for periods of 1 h and 5 h respectively. There was no significant change from controls in the level of blood glucose in both groups. Blood lactate level was significantly higher in the exercised groups but was relatively lower in the 5-h control group in comparison with its 1-h counter part. Blood lactate dehydrogenase (LDH) activity was significantly higher in the 1-h stimulated pigeons as was also the case with liver LDH in the same group but markedly lower in the 5-h ones. No significant change was seen in liver glycogen content in the stimulated pigeons. Liver phosphorylase activity was markedly low in the 5-h stimulated pigeons as was also the case with liver LDH activity. Circulating level of corticosterone was significantly higher in both the stimulated groups. Blood thyroxine (T4) as well as triiodothyronine (T3) levels were considerably reduced in both stimulated groups. The T3/T4 ratio was higher in the 5-h stimulated pigeons. It was concluded that, while initially carbohydrate was used as fuel for exercise, in prolonged exercise, lipid became the chief fuel as was shown in earlier studies. While fat continued to be used as the main fuel, carbohydrate was spared and also gluconeogenesis was enhanced. It was also concluded that the r?le of the thyroid hormones in promoting oxidative metabolism was enhanced by markedly increasing peripheral deiodination of T4 to T3 in prolonged exercise.     

Raphe nucleus and corticorophic activity in pigeons]

Multiple electrolytic lesions were placed in the raphe area of pigeons. Basal plasma corticosterone level (B) was found not to be altered. Stress-induced adrenocortical activation was markedly reduced in raphe lesioned pigeons as compared to controls. Electrical stimulation of the nucleus raphes in permanently implanted, unrestrained and unanesthetized birds induced a significant rise in B. However the magnitude of the response to raphe stimulating was lower (1/2 approximately) and especially later than after hypothalamic stimulation since it paralleled exactly the pattern of stress induced activation.     

Further studies on the effects of central administration of neuropeptide Y on neuroendocrine function in the male rat: relationship to hypothalamic catecholamines

Following intraventricular (i.v.t.) administration of increasing doses of neuropeptide Y (NPY; 7.5-750 pmol/rat) the catecholamine levels and turnover were quantitatively measured in discrete hypothalamic regions by means of histofluorometry. In the same rats the adenohypophyseal hormones as well as vasopressin, aldosterone (ALDO) and corticosterone (CORTICO) levels in serum were determined. Neuropeptide Y seems to induce a biphasic change in amine utilization in the tuberoinfundibular dopamine (DA) neurons and in the noradrenergic (NA) utilization in various hypothalamic areas. Thus, the lowest doses seem to inhibit the catecholamine utilization while higher doses seem to enhance it. NPY (250-750 pmol) reduced the serum levels of thyreotropine (TSH), prolactin (PRL) and growth hormone (GH) but increased CORTICO, adrenocorticotropin (ACTH) and ALDO serum levels. In conclusion, it is suggested that the NPY induced changes in DA utilization in the tuberoinfundibular DA neurons may contribute to the NPY induced changes in PRL and TSH secretion. The increases in paraventricular NA utilization may contribute to the increases in ACTH, ALDO and CORTICO secretion induced by NPY. These data give further support for NPY as an important neuroendocrine modulator.