Catecholamine concentration in the hypothalamus following alteration of pituitary adrenocorticotropic function]

Norepinephrine, epinephrine and serotonin levels were studied in male rabbit hypothalamus and midbrain under the influence of different factors potentiating the hypophysial adrenocorticotropic function. Intensification of this adrenohypophysial function was accompanied by a certain decrease in the hypothalamic and midbrain norepinephrine level and by the appearance of epinephrine normally absent here. The role of serotonin in the regulation of the investigated pituitary function was not revealed since potentiation of this function was observed both with the lowered and with the elevated concentrations of this monoamine in the hypothalamus.     

Effect of nitric oxide on prolactin secretion and hypothalamic biogenic amine contents

Involvement of nitric oxide (NO) in the episodic secretion of prolactin was studied in conscious freely moving adult rats. Prolactin secretion was pulsatile in all animals of either group during the bleeding period (from 10:30 h to 13:30 h). Administration of N(omega)-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, increased mean plasma levels of prolactin, and the absolute amplitude of prolactin peaks during the whole bleeding period as compared to values found in the control group. L-NAME increased norepinephrine (170%), dopamine (58.27%) and serotonin contents (30%) in the anterior hypothalamus. In the median eminence, dopamine and serotonin contents decreased (19.79% and 33.9% respectively) after L-NAME as compared to the values found in controls. In addition, norepinephrine content increased in mediobasal hypothalamus (79.6%) of rats treated with L-NAME. The results indicate that changes in NO production may modify the episodic secretion of prolactin. These effects were associated with changes in hypothalamic and median eminence biogenic amines.     

Expanded ontogeny of neurotransmitters and their metabolites in the brains of fetal and newborn lambs.

To evaluate the ontogeny of the brain neurotransmitters norepinephrine, dopamine, serotonin and the metabolites hydroxyindoleacetic acid and homovanillic acid, we measured these neurotransmitters in 10 brain areas at three ages in fetal sheep and two ages in newborn lambs. Norepinephrine exhibited an increase only at 25-30 days after birth in the midbrain, lateral hypothalamus, dorsal medial hypothalamus and ventral medial hypothalamus. Dopamine concentration was very low and did not change over the ages examined. Homovanillic acid decreased after 125 days in the cerebellum, but this change is probably not biologically meaningful, since there were no statistically significant changes in homovanillic acid in other brain areas. Serotonin increased at 25-30 days after birth in the ventral medial hypothalamus, but changes in other brain areas were not significant. Hydroxyindoleacetic acid reached its greatest concentration at 1-5 days after birth in nine of the ten brain areas examined. Thus we conclude that the serotonin system is undergoing more change in the last third of gestation and first month of extrauterine life than the norepinephrine or dopamine systems.     

Serum prolactin and brain and pituitary monoamine responses to chronic monoamine oxidase inhibition in the rat.

The acute administration of the monoamine oxidase inhibitor iproniazid to rats causes a highly significant suppression of serum prolactin levels at 2 h. At the same time there is a significant rise in the hypothalamic-median eminence concentrations of the biogenic monoamines dopamine, noradrenaline and serotonin. When iproniazid is administered daily to rats for 4 days and the animals are examined on the fifth day brain noradrenaline and serotonin levels are elevated similarly to those seen after acute administration but dopamine concentration is near normal while serum prolactin is significantly elevated. This study thus demonstrates that a quite specific and unexpected change occurs in the regulation of hypothalamic-median eminence dopamine when iproniazid is administered chronically and provides an explanation of previous observations in human subjects where raised serum prolactin levels are observed after chronic therapy with monoamine oxidase inhibitors.     

Evaluation of the necessity for rapid inactivation of brain enzymes prior to analysis of norepinephrine dopamine and serotonin in the mouse.

Norepinephrine, dopamine and serotonin concentrations were measured in mouse whole brain. Animals were killed either by decapitation or by exposure to 250 msec microwave irradiation which produces irreversible inactivation of brain enzymes. The biogenic amines were determined by mass fragmentometry, fluorometry and by a combination of high performance liquid chromatography and an electrochemical detector. No differences were found in the levels of these neurochemicals between the two methods of animal sacrifice. Therefore, rapid inactivation of brain enzymes is not necessary prior to analysis for catecholamines and serotonin in mouse whole brain.     

The regional distribution of dopamine and serotonin uptake and transmitter concentrations in the human brain

The regional distribution of the dopamine and serotonin uptake sites in human brain have been assessed and compared with the distribution of the transmitters and their metabolites measured in the same brains and also with a limited regional distribution of the uptake sites in rat and sheep brain. The affinity of the uptake sites for both transmitters was determined and found to be c. 0.2 μ M in all 3 species. Most dopamine uptake in all species was in caudate and putamen samples. Many regions of the human brain showed no dopamine uptake and little dopamine uptake was seen in sheep cortex or nigral preparations. Dopamine and metabolite concentrations were highest in the caudate, putamen and substantia nigra. Most serotonin uptake was seen in the hypothalamus in all 3 species; less was observed in the striatal regions; the cortical and nigral preparations of sheep brain showed little serotonin uptake though cortical preparations of rat brain had high levels of uptake. In the human brain, other regions did not show serotonin uptake. Highest concentrations of serotonin were found in the substantia nigra and medulla, intermediate concentrations in the putamen, globus pallidus, hypothalamus, olfactory tubercle and thalamus; very low concentrations of serotonin were found in other regions. The use of the human uptake site for pharmacological studies and as a marker for monoaminergic afferents in human health and disease is discussed.     

Monoamine and Tissue Fluid Levels in Contused Spinal Cord of Sheep

Methods are described for the determination of sheep spinal cord tissue fluid content and norepinephrine, serotonin, and dopamine concentrations after experimental injury. The amount of tissue fluid varied in different regions of sheep spinal cord following injury. Norepinephrine and serotonin wet weight concentrations were corrected for this variation in tissue fluid. Corrected norepinephrine wet weight cord concentrations did not change up to 3 hr after injury. Levels of serotonin at 60 min after injury were similar to controls. Dopamine was not detected in sheep spinal cord. α-Methyl tyrosine significantly reduced fluid in the spinal cord at 75 min after injury. Hinwood B. G. et al. Monoamine and tissue fluid levels in contused spinal cord of sheep. J. Neurochem. 35, 786–791 (1980).     

Cadmium effects on hypothalamic-pituitary-testicular axis in male rats

This study analyzes cadmium effects at the hypothalamic-pituitary-testicular axis. Male rats were given cadmium during puberty or adulthood. Cadmium exposure through puberty increased norepinephrine content in all hypothalamic areas studied, but not in the median eminence. Metal exposure increased serotonin turnover in median eminence and the anterior hypothalamus, while decreased it in mediobasal hypothalamus. Also, decreased plasma levels of testosterone were found. Cadmium exposure during adulthood increased norepinephrine content in posterior hypothalamus and decreased the neuro-transmitter content in anterior and mediobasal hypothalamus. Decreased circulating levels of luteinizing hormone (LH) and testosterone and increased plasma follicle stimulating hormone (FSH) levels were also observed. Cadmium accumulated in all analyzed tissues. Various parameters showed age-dependent changes. These data suggest that cadmium globally effects hypothalamic-pituitary-testicular axis function by acting at the three levels analyzed and that an interaction between cadmium exposure and age emerge.     

Regional Localization and Subcellular Compartmentalization of Thyrotropin-Releasing Hormone in Adult Human Brain

In the current study, we sought to define the subcellular compartmentalization of thyrotropin-releasing hormone (TRH) in adult human brain tissues. Upon evaluating tissues (3-24 h post mortem) from 62 humans, ranging in age from 5 to 75 years, we found that TRH was widely distributed throughout the brain. The highest TRH concentration (ng/mg protein) was in the stalk-median eminence region of the hypothalamus (19.3 +/- 3.3, mean +/- SE); the TRH concentration in the hypothalamus, exclusive of the stalk-median eminence, was much lower (1.7 +/- 0.2). Substantial quantities of TRH also were detected in the medulla oblongata (0.26 +/- 0.08), mammillary bodies (0.33 +/- 0.25), and optic chiasm (0.14 +/- 0.07). Lower levels of TRH were found in the amygdala (0.060 +/- 0.015) and the corpus striatum (0.033 +/- 0.010). TRH was near or below the limits of detection in tissues of the cerebral and cerebellar cortices, the olfactory bulbs, the pons, and the hippocampus. When homogenates of medial basal hypothalamic tissue (prepared in 0.32 M sucrose-10 microM CaCl2) were fractionated by means of differential centrifugation, most of the TRH was recovered in subcellular particles which were pelleted at 10,000 X g and which contained the highest amounts of occluded LDH activity. When the nuclei-free supernatant fluid (900 X g S) was fractionated on discontinuous sucrose density gradients or continuous sucrose density gradients, most of the TRH was recovered in subcellular fractions containing synaptosomes. The subcellular distribution of TRH appeared to be stable for up to 24 h post mortem in rat and human brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Post-mortem changes of neurotransmitter concentrations in the rat brain regions

Using High Performance Liquid Chromatography coupled with electrochemical detection the post-mortem stability of noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxy indole acetic acid (5-HIAA) were examined in the rat hypothalamus, amygdala, cerebral cortex, cerebellum and corpus striatum over an 8 hour time period. Changes in concentrations of the different neurotransmitters were less than it might be expected. The significant changes were: a. A fall in NA levels in the cerebral cortex by 4 hours and in the hypothalamus at 8 hours. b. A reduction in DA concentrations in the corpus striatum at 8 hours but a two fold rise of levels in the hypothalamus at 1 and 2 hours. c. A four-fold increase in 5-HT concentrations in the amygdala throughout the 8 hours studied. The results indicate that for comparative studies on post-mortem brain tissue correction factors should be employed to take into account differential changes in the concentrations of the various neurotransmitters.     

Effects of emotional stress on E1-mouse convulsions,and their biochemical background

Emotional stress markedly inhibited E1 mouse convulsions. Norepinephrine and dopamine levels in E1 mouse brain were hardly affected by stress, though a marked decrease in norepinephrine and dopamine levels was observed in the ddY mouse brain. The serotonin levels decreased in the E1 mouse brain in the same degree as in the ddY mouse brain. These findings suggest that the serotonergic system is involved in the inhibition of E1 mouse convulsions, through an enhanced serotonin release in the brain brought on by the emotional stress. Noradrenergic and dopaminergic systems may also be involved.     

Effect of interferon-alpha on tyrosine hydroxylase and catecholamine levels in the brain of rats

We investigated the effect of interferon on tyrosine hydroxylase (TH) and catecholamine levels in the brains of 12-week-old male Wistar rats. Interferon-alpha (300,000 IU/kg/day, s.c.) was administered to rats for 7 days. Locomotor activity of interferon-alpha-treated rats was significantly lower than that of control rats. Norepinephrine and dopamine levels and TH activities in the cerebral cortex, hypothalamus and medulla oblongata of interferon-alpha-treated rats were significantly higher than those of control rats. Norepinephrine and dopamine levels and TH activities in the thalamus and hippocampus were not different between interferon-alpha treated and control rats. These results suggest that interferon-alpha-induced depression may be related to change in the catecholamine synthetic pathway in the central nervous system.     

Effect of Long-Lasting Diabetes Mellitus on Rat and Human Brain Monoamines

Experimental alloxan- or streptozotocin-produced diabetes in rats was accompanied by an increase in the levels of norepinephrine, dopamine, and serotonin, whereas the contents of metabolites, i.e., 5-hydroxyindoleacetic acid and homovanillic acid, in the whole brain gradually decreased with the duration of diabetes. Among the striatum, thalamus, and hypothalamus of alloxan diabetic rats, monoamine alterations were observed only in the hypothalamus; after 1 week an increase of norepinephrine content and after 13 weeks an increase of norepinephrine and dopamine contents were found. Tissues of 11 brain regions of 10 diabetic and 12 control patients post mortem were investigated for monoamine concentrations. Patients were all male, of similar age and interval between death and autopsy. Diabetic patients had an increase in the content of serotonin in the medial and lateral hypothalamus. The content of dopamine increased in the medial hypothalamus, putamen, and medial and lateral pallidus. In diabetic patients, the content of norepinephrine increased in the lateral pallidus and decreased in the nucleus accumbens and claustrum. Thus, it seems that diabetes mellitus in rats, as well as in humans is associated with regionally specific changes in brain monoamines.     

EFFECT OF COPPER STATUS ON BRAIN NEUROTRANSMITTER METABOLISM IN THE LAMB

Abstract— Ataxic and non-ataxic lambs reared under field conditions which gave rise to low copper status were treated with copper intravenously. Untreated ataxic animals served as controls. The neurotransmitter amines, dopamine, norepinephrine and serotonin, were determined in the anterior and posterior regions of the brain stem. Dopamine levels in the anterior region, including the corpus striatum, were significantly lower in the untreated animals than in those treated with copper. Norepinephrine levels were also lower but serotonin concentrations were not different. Plasma amine oxidase activity was markedly higher in the copper treated animals but monoamine oxidase activity in brain stem homogenates was not significantly affected. The monoamine oxidase activity in cortical and cerebellar homogenates was significantly lower in the treated animals than in the untreated animals.     

Dose-related effects of cysteamine treatment on hypothalamic and striatal dopamine, noradrenaline and serotonin neurotransmission

The dose-related effects of cysteamine treatment on hypothalamic and striatal neurotransmission were investigated. Cysteamine pretreatment with a dose of 150 mg/kg slightly increased the dopamine, and markedly decreased the noradrenaline, content of the hypothalamus in a dose-related manner. The serotonin levels of the hypothalamus and striatum were not affected. Cysteamine pretreatment with a higher dose (300 mg/kg sc) slightly increased the uptake of noradrenaline into hypothalamic slices. The drug did not influence dopamine and serotonin uptake into hypothalamus and striatal slices. These results suggest that cysteamine decreases rather selectively the noradrenaline content of the hypothalamus.     

Brain corticotropin-releasing factor (CRF) and catecholamine responses in acutely stressed rats

Ether-laparotomy stress produced a rapid increase in rat hypothalamic CRF concentration, followed by a rapid reduction and subsequent increase. Cold-restraint stress significantly reduced hypothalamic CRF concentration at 15 min after stress onset. Serum ACTH and corticosterone levels were significantly elevated at 15 min after the onset of both stresses. The CRF responses in the medulla oblongata were not similar to the hypothalamic CRF responses. Norepinephrine concentration in the hypothalamus was reduced, whereas dopamine concentration in the hypothalamus and medulla oblongata was significantly increased. Epinephrine concentrations in these tissues did not show any significant change throughout the stress period. The observations lead to the following conclusions: hypothalamic CRF plays a major role in stimulating ACTH secretion under acute stress; the reduction in hypothalamic CRF is due to an excess release in the early phase of acute stress; hypothalamic CRF and medulla oblongata CRF are controlled by different mechanisms; norepinephrine in the hypothalamus may not be involved in stimulating hypothalamic CRF secretion in the early phase of acute stress; and catecholamines are regulated differently in the hypothalamus and medulla oblongata.     

Regional distribution of monoamines and monoamine metabolites in the brain of the crucian carp (Carassius carassius L.)

1. Monoamines (which all demand oxygen for their synthesis) and monoamine metabolites were quantified in 6 brain regions of the extremely anoxia tolerant crucian carp (Carassius carassius L.).2. The norepinephrine levels were generally twice as high as the dopamine levels. No epinephrine was found.3. The major dopamine metabolite seemed to be homovanillic acid. No 3,4-dihydroxyphenylacetic acid was found.4. Serotonin occurred at about the same levels as dopamine. The levels of the main serotonin metabolite, 5-hydroxyindole-3-acetic acid, were about 10% of that of serotonin.5. All three monoamines had a similar distribution, with the highest concentrations in hypothalamus and the lowest in cerebellum and vagal lobes.6. The distribution and levels of monoamines agreed with that of anamniote vertebrates in general, suggesting that the crucian carp has not adapted to anoxia by abandoning or minimizing the use of monoaminergic systems.     

Depletion of epinephrine in rat hypothalamus by a dopamine agonist,pergolide

The i.p. injection of pergolide mesylate, a dopamine agonist, at doses of 0.3–0.6 mg/kg led to a decrease in epinephrine concentration in rat hypothalamus. After a 0.6 mg/kg dose of pergolide mesylate, epinephrine concentration in hypothalamus decreased within 2 hr, reached a minimum concentration at about 8 hrs, and then returned toward control values. Norepinephrine N-methyltransferase activity was not decreased after pergolide injection in vivo nor was it inhibited by pergolide added in vitro at concentrations as high as 10^–3 M. Higher i.p. doses of less potent dopamine agonists, apomorphine (10 mg/kg) and lergotrile (3 mg/kg), also decreased epinephrine concentration in hypothalamus. The pergolideinduced decrease in hypothalamic epinephrine concentration was prevented by pretreatment with haloperidol or spiperone., antagonists of dopamine receptors. Activation of dopamine receptors appears to result in a decrease in epinephrine concentration in rat brain, possibly due to, enhanced release of epinephrine.     

Stress-induced depression of motor activity correlates with regional changes in brain norepinephrine but not in dopamine

This experiment examined how inescapable tail shock alters the level of dopamine and norepinephrine within various brain regions of the rat and the relationship of these changes to the depression of motor activity produced by the shock. Following exposure to tail shock that is known to interfere with acquisition of active behavioral tasks, animals were briefly tested for spontaneous motor activity and then sacrificed for neurochemical measures. Norepinephrine and dopamine levels in the frontal cortex, brain stem, striatum, olfactory tubercle, hypothalamus, hippocampus, septum, and amygdala were measured by a sensitive radicenzymatic technique. Exposure to 45 min of tail shock did not alter motor activity significantly, but shock sessions of 60 and 75 min duration produced a marked decrease in motor activity. Levels of dopamine were found to be very little changed in all brain regions studied except for the hypothalamus, in which a substantial rise in dopamine level was observed. Norepinephrine levels, in contrast, fell in many brain regions in response to shock. The fall in norepinephrine levels observed in twi brain regions was significantly correlated with the decline in motor activity (brain stemr=+0.70, hypothalamusr=+0.60) These data suggest that deficits in active motor behavior produced by shock parameters similar to those used in this study may reflect concomitant disturbances of noradrenergic function in specific brain regions.     

Hypothalamic sites of catecholamine inhibition of luteinizing hormone in the anestrous ewe.

Norepinephrine (NE) and dopamine (DA) actively inhibit the release of LH in anestrous ewes. This can be detected as an increase in LH pulse frequency following i.v. injection of NE and DA antagonists. The objective of this study was to determine the sites of these inhibitory actions in the ovine hypothalamus by using local administrations of the NE antagonist, phenoxybenzamine (PBZ), or the DA antagonist, pimozide (PIM), into specific hypothalamic areas. Each neurotransmitter antagonist was administered via a chronically implanted steel guide tube into either the preoptic area (POA), retrochiasmatic area (RCh), or the median eminence region (ME). Blood samples were taken every 15 min for 2 h before and 4 h during implantation of these drugs and were analyzed for LH and prolactin by RIA. Control (no treatment) samples were obtained similarly from the same animals on another day. Placement of PBZ into the POA significantly increased LH pulse frequency and mean LH concentrations over control values whereas PIM did not. In contrast, PIM significantly increased LH pulse frequency and mean LH concentrations when placed in the ME or in the RCh, but PBZ did not. No effects of PIM on prolactin concentrations were detected. These results suggest that an NE neural system operates in the POA and that a DA system acts in the medial basal hypothalamus (RCh or ME) to suppress GnRH pulse frequency in the ovary-intact anestrous ewe.