Changes In Catecholamine Levels Research Articles

Time course of the changes of catecholamine levels in rat brain during swimming stress

The time course of the changes in the levels of adrenaline, noradrenaline and dopamine was investigated in rat hypothalamus, ponsmedulla and midbrain during 4-h swimming at 35°C. The adrenaline levels showed gradual decrease whereas the noradrenaline and dopamine levels were kept in almost steady-state during the swimming. These findings suggest that brainstem adrenaline levels are not so fast adaptive as the noradrenaline and dopamine levels under the stress.

Rapid and discrete changes in hypothalamic catecholamine nerve terminal systems induced by audiogenic stress, and their modulation by nicotine — Relationship to neuroendocrine function

The effects of acute audiogenic stress, with or without simultaneous nicotine treatment (0.3 mg/kg i.v.), on catecholamine levels in discrete dopamine and noradrenaline nerve terminal systems of the hypothalamus, and on the secretion of adenohypophyseal hormones and of corticosterone, were studied using quantitative microfluorometric evaluations of catecholamine stores and radioimmunoassays for the determination of serum hormone levels. Audiogenic stress and nicotine induced very rapid and discrete decreases in noradrenaline levels in the subependymal layer (SEL), in the parvocellular part of nuc. paraventricularis hypothalamic (PA FP) and in the posterior periventricular hypothalamic systems, (PV II); the decreases were apparent 2 min following the onset of treatment. Increases of arterial blood pressure were observed after nicotine treatment but could not have been a major factor in producing the changes in catecholamine levels. These changes in NA levels may be related to the nicotine- and stress-induced increases of ACTH (SEL and PA FP) and prolactin secretion (PV II) found in the present experiments. Stress enhanced the rapid but variable increase in vasopressin secretion induced by nicotine, suggesting one possible mechanism by which stress combined with smoking can contribute to the development of increased arterial blood pressure and finally to sustained hypertension.

Ketamine, catecholamines, and uterine tone in pregnant ewes

Blood levels of ketamine, measured in both mother (1,230 ng/ml at 1 minute) and fetus (470 ng/ml at 1 minute) illustrate not only rapidly decreasing levels of the drug after its intravenous administration but also its transplacental passage. Concentrations of norepinephrine, epinephrine, and dopamine did not change in the mother or fetus after ketamine, with the exception of maternal levels of epinephrine, which were significantly higher at 45 minutes than control values (p < 0.05). Maternal effects of ketamine consisted of increases in mean arterial pressure (7% p < 0.05), cardiac output (16% p < 0.01), and respiratory acidosis, all of which were slight and transitory. Although resting uterine tone increased (39% p < 0.01), the uterine blood flow remained constant. None of the physiologic alterations could be correlated with changes in catecholamine levels. Therefore, the cardiovascular and uterine stimulating properties of ketamine at a dose of 0.7 mg/kg are small and are not the result of increased catecholamine levels in plasma. Further studies are necessary to elucidate the mechanism.

Cysteamine effects on growth hormone secretion in the male rat.

The thiol agent cysteamine (CSH) is reported to deplete immunoreactive somatostatin (SS) in the central nervous system and the gastrointestinal tract of rats. We investigated whether CSH, given sc, alters physiological GH secretion in chronically cannulated male rats. A dose of 300 mg/kg totally disrupted episodic GH secretion, causing an elevation of GH baseline levels and an absence of GH secretory bursts. CSH at a dose of 90 m/gg elevated GH trough levels and slightly reduced GH peak amplitudes, whereas a dose of 30 mg/kg did not affect episodic GH secretion. GH patterns remained disrupted in most animals on day 2 after drug administration, but returned to normal by 1 week. The administration of anti-SS serum resulted in a further elevation of GH levels in CSH-treated animals. Both clonidine and morphine induced a GH rise in treated animals. The GH response to stress was attenuated in CSH-treated animals. CSH at the highest dose given (300 mg/kg) markedly reduced norepinephrine (NE) concentrations (56% of the control value) in the hypothalamus and median eminence 4 h after administration. In the same animals, dopamine was elevated (200%) in the hypothalamus, but was unaffected in the median eminence. The changes in catecholamine levels are consistent with the hypothesis that CSH inhibits the enzyme dopamine-β-hydroxylase. Furthermore, blockade of NE synthesis with the dopamine-β-hydroxylase inhibitors diethyldithiocarbamate (500 mg/kg) or fusaric acid (100 mg/kg) completely suppressed episodic GH secretion. These findings indicate that CSH has an important effect on physiological GH secretion and that its effect is dose dependent and reversible. Lower doses appear to have a specific effect on SS-mediated inhibition of GH secretion. On the other hand, high doses of CSH totally disrupt GH secretion by affecting both the SS inhibitory and the GRF stimulatory components of episodic GH secretion. The latter action of CSH is, perhaps, mediated by both an inhibition of the synthesis of NE in the hypothalamus and an acute stress response.

Regional distribution of noradrenaline and dopamine-beta-hydroxylase in the brain of spontaneously hypertensive rats.

The catecholamine concentration and dopamine-beta-hydroxylase activity were determined in several nuclei of the brain of spontaneously hypertensive rats (SHR) compared with Wistar Kyoto (WKY) controls. Catecholamines were measured by using liquid chromatography coupled with electrochemical detection. The threshold of detection was 5 X 10(-14) mole. Dopamine-beta-hydroxylase (DBH) was assayed by a sensitive radioenzymatic assay using tyramine as the substrate. The limit of detection was 5 pmoles of octopamine per sample. Significantly lower noradrenaline content was observed in 4 week-old SHR in some medullary and hypothalamic areas which are involved in cardiovascular regulation. This abnormally was no longer detectable in 12 week-old rats. The changes in catecholamine levels observed in young rats were not observed during the development of deoxycorticosterone-salt hypertension and therefore probably do not represent a compensatory mechanism tending to limit the progressive rise blood pressure. No significant difference in DBH activity was observed between the young SHR and WKY in any brain region measured. The altered relationship between noradrenaline content and DBH activity observed in young SHR when compared to WKY suggests a change in noradrenergic neurones activity and/or structure which could correspond to a genetically transmitted neurochemical abnormality associated with the initiation of hypertension in the SHR.

HPLC determination of biogenic amines in discrete brain areas in food deprived rats

Norepinephrine (NE), dopamine (DA), 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) levels in the lateral hypothalamus (LH), ventromedial hypothalamus (VHM), median raphe (MR) and dorsal raphe (DR) were determined in nondeprived and 48 hr food deprived rats. Simultaneous determination of these compounds was accomplished by means of high performance liquid chromatography (HPLC) with electrochemical detection. When compared with controls, food deprived animals showed significant increases in 5-HT and 5-HIAA levels in the raphe nuclei, significant increases in 5-HIAA in the LH, but no changes in either 5-HT or 5-HIAA levels in the VMH. No changes in catecholamine levels were found in any of the brain areas studied. These results show that indoles in the raphe nuclei, as well as in the LH, are affected by food deprivation. The lack of change in indole levels in the VMH indicates that specific nuclei within the hypothalamus are differentially affected by food deprivation.

Effects of Bromocryptine on Hormone and Blood Pressure Levels in the Spontaneously Hypertensive Rat

SummaryTreatment of young and old male and female SH rats with bromoergo-cryptine (21 days) significantly reduced blood prolactin concentrations. Blood pressure was slightly depressed in young male SH rats whereas in females blood pressure was unchanged. Hypertension was reduced (30%) to normotensive levels in old rats of both sexes. Corticosterone levels were slightly affected by treatment. A significant drop in aldosterone levels was noted in young male SH rats exclusively. The hypotensive action of bromocryptine (a dopamine agonist) is uncertain but may be related to changes in catecholamine levels or actions within the central nervous system.

Inhibition of the in vivo biosynthesis and changes of catecholamine levels in rat brain after alpha-methyl-p-tyrosine; time- and dose-response relationships.

Male Sprague-Dawley rats were given 0.407 mmoles/kg of D,L-alpha-methyl-p-tyrosine methylester HCl (H44/68; alpha-MT) at eleven time-points between 0--24 h, or 8 doses between 0.013--1.628 mmoles/kg of the drug at 1 h before i.v. injection of 160 micronCi tyrosine-2,6-3H. The rats were killed 15 min after tyrosine-3H and brain alpha-MT, tyrosine and catecholamines (endogenous and labelled), and plasma alpha-MT and tyrosine (--3H) were chromatographically isolated before being assayed spectrophotofluorimetrically (endogenous) or by liquid scintillation methods (labelled compounds). A delayed penetration of alpha-MT from plasma into brain, different elimination rates of alpha-MT in plasma and brain, and decreasing brain/plasma drug concentration on increasing alpha-MT dosages, indicated, that alpha-MT in brain and plasma belong to different pharmacokinetic compartments. The endogenous levels of catecholamines in the time-response experiments, declined to a minimum 4 h after alpha-MT administration, where the dopamine level was 38% and the noradrenaline level 51% of the saline controls. Kinetic data of the catecholamine elimination is given. In the dose-response experiment the decrease in the endogenous catecholamine levels was dose-related up to 0.407 mmoles/kg of alpha-MT, with no further decline on higher doses. The maximal inhibition of brain catecholamine synthesis occurred within 30 min after alpha-MT administration and the inhibition correlated better with the brain than with plasma alpha-MT content. The inhibition was dose-related with a maximal synthesis inhibition of 95% for dopamine and 80% for noradrenaline at the highest dose of alpha-MT. The duration of synthesis inhibition and storage depletion were shorter for noradrenaline (12 h) than for dopamine (16 h). Further, the ED50 for synthesis inhibition of dopamine (0.057 mmoles/kg) was half of the ED50 for synthesis inhibition of noradrenaline (0.117 mmoles/kg). This might suggest different sensitivities towards alpha-MT or different availabilities of alpha-MT in the two neuron populations. At the three highest doses of alpha-MT there were signs of interference with the uptake process for tyrosine from plasma into the brain. This was indicated by increased plasma levels and decreased brain levels of tyrosine (--3H).

The role of intraneuronal amine levels in the feedback control of dopamine, noradrenaline and 5-hydroxytryptamine synthesis in rat brain

The influence of varying brain levels of dopamine, noradrenaline and 5-HT on their respective synthesis rates has been investigated. The first step in monoamine synthesis was studied in vivo by measuring the accumulation of dopa and 5-hydroxytryptophan after inhibition of the aromatic L-amino acid decarboxylase. Variations in monoamine levels were obtained by combined treatment with inhibitors of the decarboxylase (NSD 1015 or Ro 4-4602) and of monoamine oxidase (pargyline). An increase in monoamine levels by pargyline was found to inhibit the synthesis of dopamine, noradrenaline and 5-HT. Conversely, a decrease in monoamine levels induced by the decarboxylase inhibitor Ro 4-4602 appeared to stimulate dopamine and noradrenaline synthesis but had no effect on 5-HT synthesis. The influence of varying levels of dopamine and noradrenaline on the synthesis of these amines could still be demonstrated after blockade of dopamine receptos and of alpha-adrenergic (noradrenaline) receptors by haloperidol, suggesting that the mechanism involved in this feedback control is mediated via end-product inhibition of tyrosine hydroxylase. On the other hand, the stimulating influence of haloperidol on the synthesis of catecholamines does not seem to be directly related to changes in catecholamine levels. It is concluded that the short-term control of catecholamine synthesis presumably involves two independent feedback mechanisms, one intraneuronal mechanism operating via end-product inhibition, and one synaptic mechanism mediated via dopamine and noradrenaline receptors, respectively. Both pre- and postsynaptic receptors may be involved in the latter mechanism.

Changes in brain norepinephrine associated with sensitization to d-amphetamine.

Pretreatment of B6AF1/J mice with d-amphetamine HCl 10 mg/kg, twice daily for 5 days, produced a 4-fold increase in the running response to a test dose of 5 mg/kg amphetamine. Amphetamine pretreatment decreased whole-brain norepinephrine levels to 50% of control values and whole-brain dopamine to 85%. The test dose of 5 mg/kg amphetamine lowered whole brain norepinephrine levels of control mice from 0.50 mug/g to 0.28 mug/g in 2 h. In amphetamine-pretreated mice, this injection caused an increase in whole-brain norepinephrine levels from 0.22 mug/g to 0.55 mug/g at 30 min, followed by a decrease to 0.22 mug/g at 60 min. No change in whole brain dopamine levels was observed in either group. Amphetamine sensitization and norepinephrine depletion were still evident 25 days after pretreatment. No cross sensitization to morphine or cocaine was observed. Reserpine pretreatment resulted in a 3-fold increase in locomotor activity following injection of d-amphetamine, 5 mg/kg. No sensitization or changes in catecholamine levels were observed in amphetamine-treated A/J mice. These results suggest that the sensitization produced by amphetamine pretreatment may be related to the depletion of brain norepinephrine.

Behavioral effects of amphetamine in a group of rhesus monkeys with lesions of dorsolateral frontal cortex.

Four macaques with lesions of dorsolateral frontal cortex and 4 normal monkeys were injected with 1 mg/kg d-amphetamine. Observations of social behaviors and motor activity were conducted over a 1-month period. The results of this experiment show a partial dissociation of effects of amphetamines on behavior of normal and frontally lesioned animals. The frontal monkeys showed a dramatic increase in hyperactivity while normal monkeys showed a variable motor response to the drug. Conspecific social interactions were disrupted by amphetamine in normal as well as lesioned animals. A functional system featuring the caudate nucleus and dorsolateral frontal cortex is presented. In addition, the possible influence of these areas on the balance of behavior modulated by limbic structures is explored. Changes in catecholamine levels are also hypothesized.

Changes in catecholamine levels of mouse brain during oscillation-stress.

Changes in catecholamine levels of mouse brain during oscillation-stress.

On the Presence of p‐Hydroxynorephedrine in the Rat Brain and Heart in Relation to Changes in Catecholamine Levels after Administration of Amphetamine

The brain and heart NA in rats was maximally decreased by 28–52% at 3–12 hours after 20 mg/kg intraperitoneally of dl‐amphetamine‐SO4. Control levels of NA were not reached until 96 hours after a single injection of amphetamine, while the drug disappeared from the brain and plasma within 12 hours. Amphetamine was found to disappear from rat tissues in a poly‐phasic pattern after intraperitoneal administration. The brain/plasma ratio was 9.0 ± 0.3 (mean ± S. D.). Parahydroxynorephedrine was identified in the brain and heart as a metabolite of the d‐isomer of amphetamine. Parahydroxynorephedrine, the apparent T1/2 of which was estimated to be about 22 hours, seems to be responsible for the prolonged depletion in the brain and heart NA levels caused by amphetamine. However, there was not an exact stoichiometric relation between the NA deficit and the amount of p‐hydroxynorephedrine present. After pretreatment with desmethylimipramine, which inhibits the parahydroxylation of amphetamine, the NA in the brain and heart was decreased by amphetamine but already returned to control levels in about 12 hours. It is concluded that the persistent depletion of brain and heart NA induced by amphetamine is caused by the incorporation of p‐hydroxynorephedrine as a false transmitter into NA neurons.

Changes in catecholamine levels during shock in man

These results demonstrate the magnitude of the adrenergic stimulation during shock in man. Such stimulation leads to a rise in plasma catecholamines and to a relative impoverishment of the catecholamine stores in the adrenal medulla. The clinical effectiveness of this stimulation is, however, not evident in every case. From a clinical point of view, the state of shock and the subsequent hypercatecholaminaemia are not necessarily related to a severe decrease in the arterial blood pressure. On the other hand, a reduction in the urine output goes with the highest plasma catecholamine levels.

Changes in catecholamine levels during shock in man.

De ľensemble de ces résultats, on peut conclure que le systéme orthosympathique est stimulé de façon intense chez ľindividu en état de choc. Cette stimulation se marque par une hausse de la catécholaminémie sanguine accompagnée ďun appauvrissement relatif de la réserve en amines adrénergiques de la médullosurrénale. Néanmoins, ľefficacité clinique de cette stimulation n’est pas apparente dans chaque cas. Du point de vue clinique, ľétat de choc et ľhypercatécholaminémie ne sont pas nécessairement liés à une chute importante de la pression artérielle. Par contre, la réduction de la diurése accompagne les états ďhypercatécholaminémie les plus marqués.

Effects of Fasting and Refeeding. I. Studies on Sodium, Potassium and Water Excretion on a Constant Electrolyte and Fluid Intake

ABSTRACT Seventeen subjects were maintained on a constant electrolyte and fluid intake during periods of equilibration, starvation and refeeding. During 3 days of fasting, a mean daily weight loss of 800 g was accompanied by progressive natriuresis and kaliuresis without increase in urine volume. The net amount of sodium excreted as a consequence of fasting was independent of the amount of sodium supplemented. Carbohydrate refeeding induces very rapid antidiuresis of sodium and potassium. Protein has a delayed action, while fat refeeding aggravates the negative sodium balance. The sodium retaining action of carbohydrate requires a pre-existing metabolic setting induced by starvation. Bicarbonate supplementation during fasting does not alter the pattern of sodium excretion. The data suggest that the sodium retaining action of carbohydrate after brief starvation is not secondary to aldosterone, glucocorticosteroids or changes in catecholamine levels.

Observations on isoprenaline-induced myocardial necroses.

Abstract Isoprenaline hydrochloride in subcutaneous doses of 2 × 10 to 2 × 680 mg/kg caused histologically detectable, characteristic heart necroses. Pathological changes were dose-dependent. The degree of necrosis was assessed by a quantitative histological method based on counting the changed morphological elements. The heart necroses due to 2 × 40 mg/kg of isoprenaline were significantly inhibited by pretreatment with different monoamine oxidase inhibitors (iproniazid, a derivative of hydrazine and pargyline and E-250 of the non-hydrazine type, all at 7 × 50 mg/kg intraperitoneally); their severity was significantly increased by reserpine (7.5 mg/kg/48 hr subcutaneously) and guanethidine (2 × 30 mg/kg subcutaneously). In these effects an important role is attributed to respective changes in catecholamine levels.