Stress-induced Increases In Noradrenaline Turnover Research Articles

Antagonism of central CRF systems mediates stress-induced changes in noradrenaline and serotonin turnover in rat brain regions.

The present study was conducted to test the hypothesis that central corticotropin-releasing factor (CRF) systems mediate the changes in the dynamics of brain noradrenergic and serotonergic systems induced by electric footshock stress. Serum corticosterone concentrations were determined fluorometrically and brain monoamine contents (noradrenaline, serotonin and their metabolites) in five brain regions in rats were measured by high-performance liquid chromatography with electrochemical detection 10 and 40 min after exposure to electric footshock stress for 1 hour. Intracerebroventricular administration of a CRF antagonist, alpha-helical CRF (100 micrograms), had no effect on serum corticosterone concentrations in either normal or stressed animals. However, electric footshock stress-induced increases in noradrenaline turnover were significantly reduced by the administration of alpha-helical CRF9-41, in the amygdala and septum at both time points after exposure to electric footshock stress. In contrast, electric footshock stress-induced increases in serotonin turnover in all of the brain regions were further elevated by the administration of alpha-helical CRF 9-41, in almost all of the brain regions examined. These results suggest that central CRF neuronal systems are involved in mediating the electric footshock stress-induced changes in the dynamics of brain noradrenergic and serotonergic systems in rats.

A CRF antagonist attenuates stress-induced increases in NA turnover in extended brain regions in rats

We investigated the effects of intracerebroventricular (i.c.v.) administration of a corticotropin-releasing factor (CRF) antagonist, α-helical CRF 9–41 (ahCRF), on increases in noradrenaline (NA) turnover caused by immobilization stress in rat brain regions. Pretreatment with ahCRF (50 or 100 μg) significantly attenuated increases in levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO 4), the major metabolite of NA in rat brain, in the locus coeruleus (LC) region, and attenuated the MHPG-SO 4/NA ratio after immobilization stress for 50 min in the cerebral cortex, hippocampus, amygdala, midbrain and hypothalamus. However, stress-induced increases in plasma corticosterone levels were not decreased significantly by pretreatment with ahCRF. These results suggest that CRF, released during stress, causes increases in NA release in extended brain regions of stressed rats.

O-259 - Diazepam-morphine synergistic effect on stress-induced increases in noradrenaline turnover in brain regions of rats.

O-259 - Diazepam-morphine synergistic effect on stress-induced increases in noradrenaline turnover in brain regions of rats.

Expression of aggression attenuates stress-induced increases in rat brain noradrenaline turnover

This experiment determined whether or not an aggressive biting response could attenuate stress-induced increases in brain noradrenaline (NA) turnover, by measuring contents of NA and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO 4), in discrete brain regions of male Wistar rats. Rats were exposed to a 10 min supine restraint stress with or without being allowed to bite a wooden stick. In each group, the animals were sacrificed by decapitation either 0 min or 50 min after release from stress. NA and MHPG-SO 4 levels were unaffected in both biting and non-biting groups immediately after stress, as compared to controls. Fifty min after release from stress, increases in plasma corticosterone levels induced by stress recovered in the biting group but remained high in the non-biting group. MHPG-SO 4 levels significantly increased in the hypothalamus, amygdala, thalamus, midbrain, basal ganglia, hippocampus and cerebral cortex in both stressed groups, however the increases in the non-biting group were significantly higher than those in the biting group in the first 5 of these regions. These findings clearly show that giving rats an opportunity to express aggression during stress exposure results in a significant attenuation of stress-induced increases in NA turnover in specific brain regions, such as the hypothalamus and limbic areas. The present experiment provides a possible neurochemical basis for clinical studies showing that suppression of anger in a stressful, frustrating situation leads to pathological consequences in humans.

Effect of acute ethanol administration on noradrenaline metabolism in brain regions of stressed and nonstressed rats

The effects of ethanol on noradrenaline (NA) metabolism of brain regions in stressed and nonstressed rats were investigated. Male Wistar rats were injected IP with either saline, or ethanol at 0.5 g/kg or 2 g/kg, 5 min before exposure to 1-hr immobilization stress. Levels of NA and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4) in various brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant increases in MHPG-SO4 levels in all brain regions examined, i.e., the hypothalamus, amygdala, hippocampus, cerebral cortex and locus coeruleus (LC) region. In nonstressed rats, ethanol significantly increased MHPG-SO4 levels in the hypothalamus, hippocampus and cerebral cortex, but not in the amygdala or in the LC region. In stressed rats, ethanol attenuated stress-induced increases in MHPG-SO4 levels preferentially in the amygdala and LC region, but not in the remaining three regions. Although ethanol per se dose-dependently elevated plasma corticosterone levels in nonstressed rats, ethanol at 2 g/kg attenuated the stress-induced elevation of corticosterone. These results suggest that the attenuating effect of ethanol on stress-induced increases in NA turnover in the amygdala and LC region might be related to the stress-relieving properties of this drug.

Attenuating effect of diazepam on stress-induced increases in noradrenaline turnover in specific brain regions of rats: Antagonism by Ro 15-1788

One-hour immobilization stress increased levels of the major metabolite of brain nonadrenaline (NA), 3-methoxy-4-hydroxyphenyl-ethyleneglycol sulfate (MHPGSO 4), in nine brain regions of rats. Diazepam at 5 mg/kg attenuated the stress-induced increases in MHPGSO 4 levels in the hypothalamus, amygdala, hippocampus, cerebral cortex and locus coeruleus (LC) region, but not in the thalamus, pons plus medulla oblongata excluding the LC region and basal ganglia. The attenuating effects of the drug on stress-induced increases in metabolite levels in the above regions were completely antagonized by pretreatment with Ro 15-1788 at 5 or 10 mg/kg, a potent and specific benzodiazepine (BDZ) receptor antagonist. When given alone, Ro 15-1788 did not affect the increases in MHPGSO 4 levels. Behavioral changes observed during immobilization stress such as vocalization and defecation, were also attenuated by diazepam at 5 mg/kg and this action of diazepam was antagonized by Ro 15-1788 at 10 mg/kg, which by itself had no effects on these behavioral measurements. These findings suggest: (1) that diazepam acts via BDZ receptors to attenuate stress-induced increases in NA turnover selectively in the hypothalamus, amygdala, hippocampus, cerebral cortex and LC region and (2) that this decreased noradrenergic activity might be closely related to relief of distress-evoked hyperemotionality, i.e., fear and/or anxiety in animals.

O4C1524) - Met-Enkephalin inhibits stress-induced increases in noradrenaline turnover only at early stage of stress.

O4C1524) - Met-Enkephalin inhibits stress-induced increases in noradrenaline turnover only at early stage of stress.

Methionine-Enkephalin Inhibits Stress-Induced Increases in Noradrenaline Turnover in Brain Regions of Rats

Met-Enkephalin injected i.c.v. attenuated stress-induced increases in levels of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate, the major metabolite of brain noradrenaline, in the hypothalamus, amygdala, hippocampus, thalamus, midbrain and LC region in rats. The data suggest that Met-enkephalin acts to attenuate stress-induced increases in noradrenaline turnover in these brain regions in rats.

P2B0103) - Attenuating effect of diazepam on stress-induced increases in noradrenaline turnover in rat brain regions: Interaction with picrotoxin.

P2B0103) - Attenuating effect of diazepam on stress-induced increases in noradrenaline turnover in rat brain regions: Interaction with picrotoxin.

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-SO 4), in eight brain regions and plasma corticosterone levels were fluorometrically determined. Immobilization stress caused significant increases of MHPG-SO 4 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-SO 4 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.

O-22) - Inhibitory effects of opioid peptides on stress-induced increases in noradrenaline turnover in the brain regions of rats

O-22) - Inhibitory effects of opioid peptides on stress-induced increases in noradrenaline turnover in the brain regions of rats

P-368) - The effect of diazepam on stress-induced increases in noradrenaline turnover in rat brain regions

P-368) - The effect of diazepam on stress-induced increases in noradrenaline turnover in rat brain regions

Attenuating effects of morphine on stress-induced increases in noradrenaline turnover in rat brain regions - Naloxone reversal and behavioral significance

By measuring simultaneously levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-S04), in rat brain regions, we have demonstrated that morphine attenuates stress-induced increases in NA turnover selectively in the hypothalamus, amygdala,thaiamus, hippocampus and midbrain. The present study was undertaken to investigate naloxone reversal of these morphine effects and relationship between these effects and hyperemotional ity evoked by stress. Male Wistar rats were exposed to 1-hr immobilization stress. Either naloxone, 0.5 mg/kg or 5 mg/kg, or saline and morphine 6 mg/kg were injected 10 min and 5 min before stress, respectively. MHPG-S04 levels in the five brain regions were determined fluorometrically. Attenuating effects of morphine on stress-induced increases in NA turnover were antagonized by both doses of naloxone in the hypothalamus and amygdala and only by 5 mg/kg of the drug in the thalamus and hippocampus, but not by either dose in the midbrain. Naloxone at 5 mg/kg significantly enhanced struggling and defecation during 1-hr immobilization stress. In contrast, morphine, 6 mg/kg, significantly attenuated struggling, defecation, vocalization and weight loss, and these morphine actions were antagonized by 5 mg/kg of naloxone. These results further support our hypothesis indicating that endogenous opioids released during stress might act to attenuate stress-induced increases in NA turnover in specific brain regions via regionally different subtypes of opiate receptors and that these actions of opioids might be related to the relief of distress-evoked hyperemotional ity in 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-SO 4) 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-SO 4 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-SO 4 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.

Bilateral adrenalectomy does not alter stress-induced increases in noradrenaline turnover in rat brain regions.

Effects of adrenalectomy on increases in noradrenaline (NA) turnover induced by a one-hour immobilization stress were examined by measuring the levels of NA and its major metabolite, 3-methoxy-4-hydroxyphenyl-ethyleneglycol sulfate (MHPG-SO4) in specific brain regions of the rat. Bilateral adrenalectomy alone does not affect basal levels of NA and MHPG-SO4 in the brain regions examined with the exception of an increase in MHPG-SO4 levels in the hypothalamus and a decrease in NA levels in the cerebral cortex. In sham-operated rats, immobilization stress caused significant increases in MHPG-SO4 levels in five brain regions that were examined, i, e., the hypothalamus, amygdala, hippocampus, cerebral cortex and pons plus medulla oblongata, and significant decreases in NA levels in the hypothalamus and amygdala. These changes in NA and MHPG-SO4 levels induced by stress were not affected by bilateral adrenalectomy. These results suggest that corticosterone is not a causative factor in enhancing brain NA turnover during immobilization stress.

P-124 - Morphine attenuates stress-induced increases in noradrenaline turnover in specific brain regions in rats

P-124 - Morphine attenuates stress-induced increases in noradrenaline turnover in specific brain regions in rats

Stress-Induced Increases in Noradrenaline Turnover in Specific Brain Regions Are Enhanced by Naloxone Pretreatment in Rats

Stress-Induced Increases in Noradrenaline Turnover in Specific Brain Regions Are Enhanced by Naloxone Pretreatment in Rats

Reduction by propranolol of raised urinary output of MHPG in hyperactive rats

Prolonged isolation of rats resulted in hyperactivity in the open field and a significant increase in 24 hr urinary excretion of MHPG (3-methoxy-4-hydroxyphenylglycol). Exploratory activity of group-housed rats in open field was not associated with raised MHPG excretion, compared with that of rats remaining in home cages. Exposure of group-housed rats to 4°C for 2 hr also increased urinary excretion of MHPG. Pretreatment of isolated rats with dl-, d-propranolol or practolol abolished hyperactivity of isolated rats and reduced MHPG output in these rats and in rats exposed to cold. dl-Propanolol did not reduce activity of grou-housed rats in open field or their urinary excretion of MHPG. It is suggested that propranolol may have a selective inhibitory effect on stress-induced increases in noradrenaline turnover.