Brain Norepinephrine Turnover Research Articles

Potentiating effect of lithium chloride on aggressive behaviour induced in mice by nialamide plus L-DOPA and by clonidine

Effects of acute administration of LiCl on aggressive behavior and alterations in brain norepinephrine (NE), dopamine (DA) and serotonin (5-HT) contents induced by nialamide plus L-DOPA and by clonidine were examined in mice. Effects of LiCl on turnover and metabolism of brain NE were also investigated. LiCl potentiated the aggressiveness induced by both nialamide plus L-DOPA and by clonidine. Increase in levels of brain NE, DA and 5-HT by nialamide plus L-DOPA was not affected by LiCl. The potentiating effect of LiCl on clonidine aggression was not observed in mice pretreated with disulfiram. Although LiCl did not alter the steady state levels of brain NE, DA and 5-HT, it increased the turnover of NE and decreased the content of endogenous normetanephrine. These results favour the assumption that lithium reduces the ability of nerve terminal vesicles to store NE leading to an increased turnover and decreased concentration of NE at receptor sites.

Antinociceptive action of oxotremorine and regional turnover of rat brain noradrenaline, dopamine and 5-HT

In the rat, oxotremorine increases the threshold for vocalisation after-discharge (affective component of pain reactions) dose dependently at subtremor doses (30-67 mug/kg s.c.). Doses of 225-506 mug/kg were needed to elevate the thresholds for vocalisation and motor response. 1-Tryptophan, PCPA, alpha-methyl-p-tyrosine, 1-Dopa, pimozide and LSD-25 did not affect the antinociceptive activity of oxotremorine, while phenocybenzamine slightly increased the threshold for vocalisation. Oxotremorine did not change the endogenous brain concentrations of noradrenaline and dopamine or 5-HT but decreased that of 5-HIAA in all brain regions at the time of maximal analgesia. The decrease of 5-HIAA was still present after pretreatment with probenecid. After inhibition of tyrosine hydroxylase, oxotremorine accelerated the depletion of dopamine in telencephalic cortex during maximal antinociceptive activity and of noradrenaline in all brain regions at a time when this activity had vanished. Atropine significantly antagonized the analgesic activity of oxotremorine. It is concluded that oxotremorine antinociceptive activity in the rat is related to a cholinergic compoent, while a monoaminergic component is not directly involved.

Morphine-induced inhibition of different pain responses in relation to the regional turnover of rat brain noradrenaline and dopamine

The influence of morphine on different pain reactions integrated at different levels of the central nervous system was studied in rats together with the determination of the turnover rate of noradrenaline and dopamine in discrete areas of the brain. Morphine was found to increase the thresholds for vocalisation and vocalisation afterdischarge leaving the threshold for motor response unaffected. The effect of morphine on the threshold for vocalisation was found to be antagonized by naloxone and yohimbine and increased by α-methyl-p-tyrosine, FLA 63, phenoxybenzamine, chlorpromazine and pimozide. The effects on the threshold for vocalisation afterdischarge were antagonized by naloxone, and reduced by α-methyl-p-tyrosine, pimozide and chlorpromazine and were enhanced by phenoxybenzamine and yohimbine. Atropine did not change the morphine effect on either threshold. Morphine (5 mg/kg s.c.) was found to increase the turnover rate of dopamine in the telencephalic cortex and the diencephalons-mesencephalon-striatum and that of noradrenaline in the medulla oblongata-pons region. Both increases were antagonized by naloxone. The ability of morphine to increase the threshold for vocalisation afterdischarge (proposed to reflect the emotional component of pain reactions) is suggested to be closely related to the increased turnover of dopamine in limbic structures of the brain, most probably by an increased release of this transmitter. The effect of morphine on the threshold for vocalisation remains to be evaluated but a decreased activity of noradrenaline and dopamine neurotransmission was found to increase the morphine effect on this threshold.

The effects of acutely administered analgesics on the turnover of noradrenaline and dopamine in various regions of the rat brain.

1 Noradrenaline and dopamine turnover rates were determined following blockade of synthesis by alpha-methyl-p-tyrosine. Morphine, pentazocine and methadone had no effect on steady state levels or on turnover of noradrenaline in whole brain and in the hypothalamus. Although morphine was without action on medulla-pons noradrenaline steady state levels, a drug-induced increase in turnover rate was observed which was antagonized by pretreatment with naloxone (5 mg/kg). Pentazocine and methadone failed to alter either the steady state level of noradrenaline in the medulla-pons or its turnover rate.2 Morphine accelerated the decline in striatal alpha-methyl-m-tyramine levels following subcutaneous injection of alpha-methyl-m-tyrosine 18 h previously.3 All three drugs increased the turnover of dopamine in whole brain and corpus striatum although the striatal effect was prevented by naloxone pretreatment. The minimum doses of morphine, pentazocine and methadone required to elicit a significant effect on striatal dopamine turnover were 10 mg/kg, 30 mg/kg and 10 mg/kg respectively.4 The possibility of a dopaminergic involvement in the antinociceptive effect of analgesics is discussed.

Time-dependent changes in brain biogenic amine dynamics following castration in male rats.

Abstract—Alterations in whole‐brain and hypothalamic levels of serotonin (5‐HT), 5‐hydroxyindoleacetic acid (5‐HIAA), norepinephrine (NE), dopamine (DA) as well as the turnover rates of NE and DA of adult male rats were analysed fluorometrically at either 3 weeks or 6 weeks following castration. Significant increases were observed in whole‐brain (minus hypothalamus) 5‐HIAA levels and hypothalamic DA levels, fractional rate constants and utilization rates at the 3 but not the 6 week intervals. Elevated levels of 5‐HT were observed at both time intervals while an increase in whole‐brain DA was seen only at the 6 week interval. Whole brain NE turnover rates of castrated animals did not differ significantly from those of sham‐castrate control animals at either test interval. However, a tendency toward increased hypothalamic NE turnover rates was seen in the castrated animals. These biochemical changes resulted in decreased NE/5‐HT and DA/5‐HT ratios for the castrate rats as compared to controls.The results are discussed in relation to emotional and aggressive behavior and are interpreted as being consistent with the hypothesis purporting an inhibitory role for 5‐HT and excitatory role for NE and DA in sex‐specific behavior patterns including aggression.

Social environment and brain biogenic amine metabolism in rats.

Abstract : The effects of living alone or in groups of three for four weeks on brain biogenic amine metabolism was investigated in rats. Isolation produced an increase in brain norepinephrine turnover relative to the grouped subjects. In addition, reserpine and para-chlorophenylalanine treatment affected brain norepinephrine levels more after isolation than after grouped housing. Brain serotonin metabolism showed minimal changes in differentially housed rats. These findings are in direct contrast to results from studies on psychosocial determinants of brain amine metabolism in mice. (Author)

Effect of four amphetamines on brain biogenic amines and their metabolites

The effect of D-amphetamine, D-methylamphetamine, p-nitro and p-bromomethylamphetamine on the release and turnover (as assessed by synthesis blockade) of brain noradrenaline and 5-HT have been studied in the rat. All the amphetamines increased the turnover of brain 5-HT but their mechanism of action in reducing the level of this amine appeared to differ. Thus methylamphetamine and p-nitromethylamphetamine potentiated the effect of 4-methyl-α-ethyl-meta-tyramine in depleting brain 5-HT, whereas the other two amphetamines were without effect. Similarly both methyl and p-nitromethylamphetamine significantly decreased the turnover of brain noradrenaline whereas the other amphetamines were without effect. The effect of these drugs on the noradrenaline, dopamine, 5-HT, normetanephrine and 5-hydroxyindole acetic acid concentration in the cortex, middle brain and caudal brain regions were also studied. p-Bromomethylamphetamine appeared to be unique in that it only affected the normetanephrine and 5-hydroxyindole acetic acid content of the middle brain region. The other amphetamines affected the metabolism of the biogenic amines in at least two of the three brain regions studied. These findings are discussed with respect to the different behavioural effects produced in animals by these drugs.

Some effects of caffeine and aminophylline on the turnover of catecholamines in the brain.

Abstract The effect of caffeine and aminophylline on the turnover of noradrenaline and dopamine in the mouse brain was studied by two different methods: estimation of the rate of disappearance of the transmitter after inhibition of synthesis and measurement of the accumulation of [3H]noradrenaline (3H-NA) and [3H]dopamine (3H-DA) after administration of [3H]tyrosine. After inhibition of the tyrosine hydroxylase the xanthines had little or no effect on the disappearance of both catecholamines. After inhibition of dopamine β-hydroxylase, both xanthines increased the rate of disappearance of noradrenaline. When given in sufficiently large doses both xanthines increased the yield of 3H-NA and 3H-DA from [3H]tyrosine. Pretreatment with a monoamine oxidase inhibitor caused a decrease in the yield of the tritiated catecholamines, which could be counteracted by the xanthines. Stimulation of the noradrenaline receptors by clonidine appeared to cause a decrease in the yield of 3H-NA and an increase in the amount of 3H-DA formed from [3H]tyrosine. Conversely, stimulation of the dopamine receptors by apomorphine caused a decrease in the yield of 3H-DA and an increase in that of 3H-NA. Also, in caffeine-treated animals, clonidine and apomorphine decreased the yield of 3H-NA and 3H-DA respectively. However clonidine could not increase 3H-DA concentrations, nor apomorphine the 3H-NA concentrations more than did caffeine alone. Thus, caffeine and aminophylline appear to increase the rate of turnover of both catecholamines in the brain.

A reduced rate of turnover of brain noradrenaline during pentobarbitone anaesthesia.

Journal Article A reduced rate of turnover of brain noradrenaline during pentobarbitone anaesthesia Get access Torgny Persson, Torgny Persson Psychiatric Research Centre, s:t Jörgen Hospital, Department of Pharmacology, University of Göteborg, Sweden Search for other works by this author on: Oxford Academic Google Scholar Bertil Waldeck Bertil Waldeck Psychiatric Research Centre, s:t Jörgen Hospital, Department of Pharmacology, University of Göteborg, Sweden Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 23, Issue 5, May 1971, Pages 377–378, https://doi.org/10.1111/j.2042-7158.1971.tb09931.x Published: 12 April 2011 Article history Received: 03 February 1971 Published: 12 April 2011

Persistent Alteration of Turnover of Brain Noradrenaline in the Offspring of Rats subjected to Stress during Pregnancy

VARIOUS hypotheses have suggested that environmental stress during development is an aetiological factor in mental illnesses. Such hypotheses have included both biological and psychoanalytical concepts, but they have not explained convincingly any possible mechanism of action of stress. The developing organism has often been shown to be sensitive to various hormonal influences, and steroid and thyroid hormones or stress, given at a critical time during the neonatal period, seem to affect permanently the behaviour and metabolism of growing animals1–3.

Effects of L-Dopa on Norepinephrine Metabolism in the Brain

Rats received intracisternal [(3)H]norepinephrine and, after 5 min, intraperitoneal L-dopa (100 mg/kg); they were killed at intervals during the subsequent 24 hr. Their brains were assayed for norepinephrine, L-dopa, S-adenosylmethionine, and [(3)H]norepinephrine and its metabolites. Rats that received L-dopa had markedly lower brain concentrations of S-adenosylmethionine and of O-methylated metabolites of [(3)H]norepinephrine than controls. An increase (15-40%) in brain norepinephrine content and accelerated turnover of brain norepinephrine was also observed in the animals receiving L-dopa. These changes were all transient, lasting about 1 hr and coinciding with the period when appreciable amounts of L-dopa were detectable in the brain.

Influence of chronic administration of nicotine on the turnover and metabolism of noradrenaline in the rat brain.

Chronic administration of nicotine (0.5 mg/kg, subcutaneously, 3 to 5 times a day for 6 weeks) accelerated the rate of disappearance of intraventricularly administered 3H-noradrenaline from rat brain. This was associated with normal levels of 3H-normetanephrine suggesting an increase in intraneuronal deamination. The rate constant of amine decline (k) in animals chronically treated with nicotine was significantly greater than that of controls, while the steady state level of brain noradrenaline was about equal in both groups of rats. Amphetamine, reserpine, acetylcholine, histamine, pheniprazine, pargyline, and nicotine affected the catecholamine levels in the rat brain treated with nicotine to the same degree as they did in the controls. It is concluded that chronic administration of nicotine may increase noradrenaline turnover in the brain and possibly increase the deamination of this amine.

Norepinephrine turnover in brain and stress reactions in rats during paradoxical sleep deprivation

An increased catabolism of exogenous norepinephrine was observed in the brains of rats subjected either to total sleep deprivation or to close confinement on flower pots without abolition of paradoxical sleep. This suggested that the observed metabolic change was not a consequence of paradoxical sleep deprivation and it seemed possible that stress reactions were occuring. This hypothesis was tested by examining adrenal gland weights and plasma corticosterone levels.

The effects of lthium salts on the turnover and metabolism of norepinephrine in rat brain.

Acute or chronic administration of lithium chloride increased the disappearance of intracisternally administered norepinephrine-H3 from rat brain. Tritiated deaminated catechol metabolites and free deaminated-O-methylated metabolites represented a larger fraction of the radioactivity present in the brain in animals treated with lithium chloride than in control animals. Statistically significant changes in the uptake of norepinephrine-H3 into brain were not observed after the chronic administration of lithium chloride. The findings suggest that chronic, as well as acute administration of lithium salts may increase norepinephrine turnover in brain and possibly increase the deamination of this amine.

Effect of chronic cold stress on catecholamine levels in rat brain.

Acute stress of various types (foot shock, exposure to cold, etc.) has been shown to reduce the endogenous content of norepinephrine in the brain. On the contrary, the present study indicates that chronic stress produced by exposing rats to cold for 6 h a day for twenty days induced elevated level of endogenous catecholamines in the brain. Also, there was increase in initial accumulation of H3-norepinephrine and increase in turn-over rate of norepinephrine in the brain. It seems that repeated exposure to cold may have induced adaptive changes in physiologic system resulting in acceleration of brain norepinephrine turnover.

Evidence for a central 5-hydroxytryptamine receptor stimulation by lysergic acid diethylamide.

1. Lysergic acid diethylamide (LSD) and the 5-hydroxytryptamine (5-HT) precursor, 5-hydroxytryptophan produced similar functional effects in rat spinal cord and brain to the 5-hydroxytryptamine precursor 5-hydroxytryptophan, which indicates that LSD stimulates central 5-HT receptors.2. By means of combined histochemical and biochemical techniques it was found that LSD reduced the turnover rate of brain and spinal cord 5-HT, studied after inhibition of the tryptophan hydroxylase by alpha-propyldopacetamide. The turnover of brain noradrenaline but not dopamine was somewhat accelerated.3. The functional and chemical effects by LSD were related to dose and to time. They were not observed after the LSD analogues 2-bromo-LSD and methylsergide.4. The retardation of the 5-HT turnover by LSD may be due to negative feed-back mechanisms evoked by direct stimulation of the central 5-HT receptors.