Tannins from Terminalia chebula fruits attenuates GABA antagonist-induced anxiety-like behaviour via modulation of neurotransmitters.

OBJECTIVES: This article investigates the anxiolytic activity of Terminalia chebula tannin-rich extract against picrotoxin (PTX; GABA antagonist)-induced anxiety in mice model. METHODS: Anxiolytic activity was studied by elevated plus maze (EPM), open field test (OFT), light/dark box test (LDT) and Vogel's conflict test (VCT). Electroencephalogram (EEG) was performed to know the changes in brain activity instigated by GABA antagonist. 5-hydroxytryptamine (5-HT), dopamine and norepinephrine levels in brain tissues were estimated by HPLC. The mRNA (CREB, BDNF, GABA, and 5-HT1A ) and protein expression (CREB, p-CREB, BDNF, ERK ½, p-ERK ½, GABAA Rα1, 5-HT1A and GAPDH) levels in brain tissue were determined by RT-PCR and Western blot analysis, respectively. KEY FINDINGS: Terminalia chebula tannin-rich extract (TCHE) supplementation increased locomotion in mice towards open arm (EPM), time spent in illuminated area (LDT), rearing frequency (OFT) and number of shocks (VCT) compared to PTX (P < 0.05). Furthermore, TCHE down-regulated serum cortisol levels and showed increased levels of 5-HT, DA and NE. Gene expressions such as BDNF, CREB, GABAA and 5-HT1A were up-regulated by TCHE treatment compared to PTX. CONCLUSIONS: Terminalia chebula tannin-rich extract showed significant anxiolytic activity against picrotoxin and could be used as natural therapy in neurodegenerative disorders.

Glutamate Promotes Contraction of the Rat Ductus Arteriosus.

BACKGROUND: Extremely preterm infants frequently have patent ductus arteriosus (PDA). Recent recommendations include immediately beginning amino acid supplementation in extremely preterm infants. However, the effect of amino acids on closure of the ductus arteriosus (DA) remains unknown.Methods and Results:Aminogram results in human neonates at day 2 revealed that the plasma glutamate concentration was significantly lower in extremely preterm infants (<28 weeks' gestation) with PDA than in those without PDA and relatively mature preterm infants (28-29 weeks gestation). To investigate the effect of glutamate on DA closure, glutamate receptor expression in fetal rats was examined and it was found that the glutamate inotropic receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type subunit 1 (GluR1), mRNA was highly expressed in the DA compared to the aorta on gestational day 19 (preterm) and gestational day 21 (term). GluR1 proteins were co-localized with tyrosine hydroxylase-positive autonomic nerve terminals in the rat and human DA. Intraperitoneal administration of glutamate increased noradrenaline production in the rat DA. A whole-body freezing method demonstrated that glutamate administration induced DA contraction in both preterm (gestational day 20) and term rat fetuses. Glutamate-induced DA contraction was attenuated by the calcium-sensitive GluR receptor antagonist, NASPM, or the adrenergic receptor α1 blocker, prazosin. CONCLUSIONS: These data suggest that glutamate induces DA contraction through GluR-mediated noradrenaline production. Supplementation of glutamate might help to prevent PDA in extremely preterm infants. (Circ J 2016; 80: 2388-2396).

Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?

Severe systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin can also be administered to raise mean arterial pressure or decrease the norepinephrine dose. Endogenous norepinephrine and vasopressin are synthesised by the copper-containing enzymes dopamine ß-hydroxylase and peptidylglycine α-amidating monooxygenase, respectively. Both of these enzymes require ascorbate as a cofactor for optimal activity. Patients with severe sepsis present with hypovitaminosis C, and pre-clinical and clinical studies have indicated that administration of high-dose ascorbate decreases the levels of pro-inflammatory biomarkers, attenuates organ dysfunction and improves haemodynamic parameters. It is conceivable that administration of ascorbate to septic patients with hypovitaminosis C could improve endogenous vasopressor synthesis and thus ameliorate the requirement for exogenously administered vasopressors. Ascorbate-dependent vasopressor synthesis represents a currently underexplored biochemical mechanism by which ascorbate could act as an adjuvant therapy for severe sepsis and septic shock.

Orexigenic effects of omentin-1 related to decreased CART and CRH gene expression and increased norepinephrine synthesis and release in the hypothalamus.

Omentin-1, a visceral fat depot-specific secretory protein, is inversely correlated with obesity and insulin resistance. We investigated, in rats, the effects of chronic omentin-1 administration (8 µg/kg, intraperitoneally, once daily for 14-days) on feeding behavior and related hypothalamic peptides and neurotransmitters. Food intake and body weight were recorded daily throughout the study. We found a significantly increased food intake compared to controls, but only in days 10-14, while body weight significantly increased since day 12 (P<0.05). Compared with vehicle, omentin-1 treatment led to a significant reduction in both cocaine and amphetamine-regulated transcript (CART) (P<0.05) and corticotrophin releasing hormone (CRH) (P<0.05) gene expression, while pro-opiomelanocortin (POMC), agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A gene expression were not modified with respect to vehicle-treated rats. We also found an increase in hypothalamic levodopa (l-dopa) (P<0.05) and norepinephrine (NE) (P<0.01) synthesis, without any effect on dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) metabolism. Furthermore, in hypothalamic synaptosomes, omentin-1 (10-100 ng/ml) stimulated basal NE release (ANOVA, P<0.0001; post hoc, P<0.001 vs. vehicle), in a dose-dependent manner, leaving unaffected both basal and depolarization-induced DA and 5-HT release. Finally, when synaptosomes were co-perfused with leptin and omentin-1, we observed that leptin was able to reverse omentin-1-induced stimulation of NE. In conclusion, the orexigenic effects of omentin-1 could be related, at least in part, to decreased CART and CRH gene expression and increased NE synthesis and release in the hypothalamus.

Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells.

Ascorbic acid is well known to acutely stimulate norepinephrine synthesis in neurosecretory cells, but it has also been shown over several days to increase tyrosine hydroxylase mRNA and norepinephrine synthesis in cultured neurons. Since tyrosine hydroxylase is the rate-limiting step in catecholamine synthesis, an effect of ascorbate to increase tyrosine hydroxylase protein could contribute to its ability to increase or sustain catecholamine synthesis. Therefore, we evaluated whether tyrosine hydroxylase protein expression and function is increased in SH-SY5Y neuroblastoma cells by physiologically relevant intracellular ascorbate concentrations. SH-SY5Y neuroblastoma cells did not contain ascorbate and had only very low levels of norepinephrine in culture with L-tyrosine, the substrate for tyrosine hydroxylase. However, treatment of cells with ascorbate for 6 h or more markedly increased norepinephrine synthesis, such that intracellular ascorbate and norepinephrine increased in parallel with half maximal intracellular concentrations of about 1 mM ascorbate and 150 µM norepinephrine. This increase was enhanced by supplementing tetrahydrobiopterin, but was not mimicked by several antioxidants or by catalase or superoxide dismutase. Tyrosine hydroxylase protein expression increased at intracellular ascorbate concentrations above 1.5 mM. This contributed to norepinephrine generation, which was decreased 50-60% by inhibition of protein synthesis with cycloheximide at high intracellular ascorbate. These results suggest that expected physiologic neuronal ascorbate concentrations enhance norepinephrine synthesis both by maintaining tetrahydrobiopterin and increasing tyrosine hydroxylase expression.

Mechanism of hot flashes.

Hot flashes are a common and disturbing adverse effect of hormonal therapy for cancer. Their pathophysiology is poorly understood. At present, the leading mechanistic hypothesis rests on the assumption that abrupt hormone deprivation will result in loss of negative feedback over hypothalamic noradrenaline synthesis. In this article we critically review the different theories used to explain this phenomenon. A better understanding of the pathophysiology of hot flashes may facilitate the development of new therapeutic approaches.

Mechanism of hot flashes

Hot flashes are a common and disturbing adverse effect of hormonal therapy for cancer. Their pathophysiology is poorly understood. At present, the leading mechanistic hypothesis rests on the assumption that abrupt hormone deprivation will result in loss of negative feedback over hypothalamic noradrenaline synthesis. In this article we critically review the different theories used to explain this phenomenon. A better understanding of the pathophysiology of hot flashes may facilitate the development of new therapeutic approaches (AU)

Expression of the paralogous tyrosine hydroxylase encoding genes th1 and th2 reveals the full complement of dopaminergic and noradrenergic neurons in zebrafish larval and juvenile brain.

The development of dopaminergic and noradrenergic neurons has received much attention based on their modulatory effect on many behavioral circuits and their involvement in neurodegenerative diseases. The zebrafish (Danio rerio) has emerged as a new model organism with which to study development and function of catecholaminergic systems. Tyrosine hydroxylase is the entry enzyme into catecholamine biosynthesis and is frequently used as a marker for catecholaminergic neurons. A genome duplication at the base of teleost evolution resulted in two paralogous zebrafish tyrosine hydroxylase-encoding genes, th1 and th2, the expression of which has been described previously only for th1. Here we investigate the expression of th2 in the brain of embryonic and juvenile zebrafish. We optimized whole-mount in situ hybridization protocols to detect gene expression in the anatomical three-dimensional context of whole juvenile brains. To confirm whether th2-expressing cells may indeed use dopamine as a neurotransmitter, we also included expression of dopamine beta hydroxylase, dopa decarboxylase, and dopamine transporter in our analysis. Our data provide the first complete account of catecholaminergic neurons in the zebrafish embryonic and juvenile brain. We identified four major th2-expressing neuronal groups that likely use dopamine as transmitter in the zebrafish diencephalon, including neurons of the posterior preoptic nucleus, the paraventricular organ, and the nuclei of the lateral and posterior recesses in the caudal hypothalamus. th2 expression in the latter two groups resolves a previously reported discrepancy, in which strong dopamine but little tyrosine hydroxylase immunoreactivity had been detected in the caudal hypothalamus. Our data also confirm that there are no mesencephalic DA neurons in zebrafish.

Increased release of serotonin in the spinal cord during low, but not high, frequency transcutaneous electric nerve stimulation in rats with joint inflammation.

OBJECTIVE: To determine the release pattern of serotonin and noradrenaline in the spinal cord in response to transcutaneous electric nerve stimulation (TENS) delivered at low or high frequency. DESIGN: Prospective randomized allocation of 3 treatments. SETTING: Research laboratory. ANIMALS: Male Sprague-Dawley rats (weight range, 250-350 g). INTERVENTION: Knee joints of rats were inflamed with a mixture of 3% carrageenan and 3% kaolin for 24 hours prior to placement of push-pull cannulae into the dorsal horn of the spinal cord. Push-pull samples were collected in 10-minute intervals before, during, and after treatment with low-frequency TENS (4 Hz), high-frequency TENS (100 Hz), or sham TENS. TENS was applied to the inflamed knee joint for 20 minutes at sensory intensity and 100-mus pulse duration. Push-pull samples were analyzed for serotonin and noradrenaline by high performance liquid chromatography with coulemetric detection. MAIN OUTCOME MEASURES: Spinal concentrations of serotonin and noradrenaline. RESULTS: Low-frequency TENS significantly increased serotonin concentrations during and immediately after treatment. There was no change in serotonin with high-frequency TENS, nor was there a change in noradrenaline with low- or high-frequency TENS. CONCLUSIONS: Low-frequency TENS releases serotonin in the spinal cord to produce antihyperalgesia by activation of serotonin receptors.

Nitric oxide modulation of norepinephrine production in acupuncture points.

The purpose of this study was to examine the levels of norepinephrine (NE) turnover in skin tissues and to determine the effect of nitric oxide (NO) on NE production in acupuncture points (acupoints) and meridians. The rats were pretreated with alpha-methyl-tyrosine methyl ester and intravenously infused with L-(2,3,5,6-(3)H)-tyrosine. Blood was withdrawn and skin tissues were excised from the low skin resistance points, non-acupoint, and non-meridian areas located on leg, arm, or trunk. The results showed that the skin NE concentration and (3)H-NE release in acupoints were significantly higher than those in non-acupoints and non-meridian controls. (3)H-NE releases in the acupoints were increased by intravenous infusion of 2-N,N-diethylamino-diazenolate-2-oxide, an NO donor, but lowered by N(G)-Propyl-L-arginine, an inhibitor of neuronal NO synthesis. NE turnover rates in the acupoints were lower in the NO donor treated group while the inhibitor of NO synthesis reversed the trend. In contrast, NE turnover rates were not altered by NO donor and inhibitor of NO synthesis in non-acupoint and non-meridian control tissues. This is the first evidence that NE turnover was consistently decreased in acupoints and enhanced NE synthesis/release in acupoints were facilitated by presence of an NO donor and inhibited by an inhibitor of NO synthesis. The data suggest that skin NE synthesis/release in acupoints/meridians is increased in skin acupoints, which is modulated by L-arginine-derived NO synthesis in sympathetic nervous system.

Bee venom injection significantly reduces nociceptive behavior in the mouse formalin test via capsaicin-insensitive afferents.

UNLABELLED: Peripheral bee venom (BV) administration produces 2 contrasting effects, nociception and antinociception. This study was designed to evaluate whether the initial nociceptive effect induced by BV injection into the Zusanli acupoint is involved in producing the more prolonged antinociceptive effect observed in the mouse formalin test, and whether capsaicin-sensitive primary afferents are involved in these effects. BV injection into the Zusanli point increased spinal Fos expression but not spontaneous nociceptive behavior. BV pretreatment 10 minutes before intraplantar formalin injection dose-dependently attenuated nociceptive behavior associated with the second phase of the formalin test. The destruction of capsaicin-sensitive primary afferents by resiniferatoxin (RTX) pretreatment selectively decreased BV-induced spinal Fos expression but did not affect BV-induced antinociception. Furthermore, BV injection increased Fos expression in tyrosine hydroxylase immunoreactive neurons in the locus caeruleus, and this expression was unaltered by RTX pretreatment. Finally, BV's antinociception was blocked by intrathecal injection of 10 microg idazoxan, and this effect was not modified by RTX pretreatment. These findings suggest that subcutaneous BV stimulation of the Zusanli point activates central catecholaminergic neurons via capsaicin-insensitive afferent fibers without induction of nociceptive behavior. This in turn leads to the activation of spinal alpha2-adrenoceptors, which ultimately reduces formalin-evoked nociceptive behaviors. PERSPECTIVE: This study demonstrates that BV acupuncture produces a significant antinociception without nociceptive behavior in rodents, which is mediated by capsaicin-insensitive afferents and involves activation of central adrenergic circuits. These results further suggest that BV stimulation into this acupuncture point might be a valuable alternative to traditional electrical or mechanical acupoint stimulation.

Impaired autofeedback regulation of hypothalamic norepinephrine release in experimental uremia.

Chronic renal failure (CRF) is associated with multiple hypothalamic dysfunctions, including reduced secretion of gonadotropin-releasing hormone (GnRH). Because GnRH release is tightly controlled by sympathetic neuronal input, a possible alteration of local noradrenergic neurotransmission in experimental CRF was evaluated. Basal, stimulated, and autoinhibited norepinephrine (NE) release was assessed in hypothalamic and hippocampal tissue slices obtained from 5/6-nephrectomized and control rats. Autoinhibition-free NE release from brain slices, prelabeled with [3H]NE and superfused with physiologic buffer, was stimulated by six electrical pulses, 100 Hz (pseudo-one-pulse stimulation). Autoinhibited NE release was induced by 90 pulses at 3 Hz. The release of tritiated NE was measured upon addition of increasing concentrations of unlabeled NE to exogenously activate the inhibitory alpha2-autoreceptor. Although neither basal nor stimulated NE release differed between the groups, significantly lower pIC50 and Imax estimates of the concentration-response curves of exogenous NE on [3H]NE release were observed in CRF rats, suggesting a diminished autoinhibition of hypothalamic noradrenergic terminals in CRF. Western blotting of tissue homogenates disclosed a significantly reduced abundance of alpha2-autoreceptor protein in hypothalamic tissue from CRF rats. These abnormalities were selectively observed in the hypothalamus, whereas noradrenergic autoinhibition seemed unaltered in the hippocampus. The results suggest a diminished autoinhibition of hypothalamic NE release in CRF. Although impaired hypothalamic NE autoinhibition does not explain reduced GnRH secretion in CRF, it may be involved in the pathogenesis of sympathetic hyperactivity associated with this condition.

Postnatal regulation by monoamines of vasopressin expression in the neuroendocrine hypothalamus of MAO-A-deficient mice.

We studied the influence of noradrenaline (NA) and serotonin (5-HT) on arginine-vasopressin (AVP) expression in the mouse neuroendocrine hypothalamus during the postnatal period. We used 11-day-old transgenic Tg8 mice knock-out for the monoamine oxidase A gene, which are characterized by increased amounts of NA (two-fold) and 5-HT (nine-fold) in the brain compared with wild-type littermates. AVP expression, determined by enzyme immunoassay and in situ hybridization, was increased in the suprachiasmatic nucleus (SCN), decreased in the supraoptic nucleus (SON), and unchanged in the paraventricular nucleus of Tg8 mice compared with wild-types. Inhibiting NA synthesis by injecting alpha-methylparatyrosine to Tg8 mice, AVP levels were decreased in the SCN but increased in the SON. Moreover, the administration of parachlorophenylalanine, a 5-HT synthesis inhibitor, was associated with increased AVP contents in the SCN only. Together, these data show a marked region-specific sensitivity of AVP expression to NA and 5-HT during the postnatal period in the mouse hypothalamus.

The effects of music listening after a stressful task on immune functions, neuroendocrine responses, and emotional states in college students.

The purpose of this study was to examine the effects of listening to high-uplifting or low-uplifting music after a stressful task on (a) immune functions, (b) neuroendocrine responses, and (c) emotional states in college students. Musical selections that were evaluated as high-uplifting or low-uplifting by Japanese college students were used as musical stimuli. Eighteen Japanese subjects performed stressful tasks before they experienced each of these experimental conditions: (a) high-uplifting music, (b) low-uplifting music, and (c) silence. Subjects' emotional states, the Secretory IgA (S-IgA) level, active natural killer (NK) cell level, the numbers of T lymphocyte CD4+, CD8+, CD16+, dopamine, norepinephrine, and epinephrine levels were measured before and after each experimental condition. Results indicated low-uplifting music had a trend of increasing a sense of well-being. High-uplifting music showed trends of increasing the norepinephrine level, liveliness, and decreasing depression. Active NK cells were decreased after 20 min of silence. Results of the study were inconclusive, but high-uplifting and low-uplifting music had different effects on immune, neuroendocrine, and psychological responses. Classification of music is important to research that examines the effects of music on these responses. Recommendations for future research are discussed.

R-fluoxetine increases extracellular DA, NE, as well as 5-HT in rat prefrontal cortex and hypothalamus: an in vivo microdialysis and receptor binding study.

The selective serotonin reuptake inhibitor fluoxetine consists of equal amounts of R and S stereoisomers. In this study, we investigated the pharmacologic properties of the stereoisomers using transporter and receptor binding assays and in vivo microdialysis in freely moving rats. Binding to the transporter confirmed selectivity of R- and S-fluoxetine for the 5-HT transporter versus the dopamine (DA) and norepinephrine (NE) human transporters. Receptor binding studies demonstrated significant affinity of R-fluoxetine, but not S-fluoxetine, for human 5-HT(2A) and 5-HT(2C) receptor subtypes. Functional GTPgammaS binding studies indicated that R-fluoxetine is an antagonist at 5-HT(2A) and 5-HT(2C) receptors. In microdialysis studies, acute R- and S-fluoxetine increased extracellular levels of 5-HT, DA, and NE in prefrontal cortex (PFC), but R-fluoxetine caused significantly greater increases of catecholamines. R-fluoxetine increased extracellular levels of 5-HT and NE in PFC, nucleus accumbens, and hypothalamus, whereas it increased dopamine in PFC and hypothalamus, but not in DA-rich nucleus accumbens and striatum, thus indicating a regionally selective effect. The unexpected increases of extracellular catecholamines by a selective 5-HT uptake inhibitor like R-fluoxetine may be due to its antagonism of 5-HT(2C) receptors.

Intracerebroventricular injection of glucagon-like peptide-1 decreases monoamine concentrations in the hypothalamus of chicks.

1. We measured the concentrations of dopamine (DA), norepinephrine (NE), epinephrine (E) and 5-hydroxytryptamine (5-HT) in the hypothalamus of 21-d-old male brown-egg layer-type chicks after intracerebroventricular injection of glucagon-like peptide-1 (GLP-1). 2. The monoamine concentrations of the whole hypothalamus, paraventricular nucleus and lateral hypothalamic area were not significantly affected by GLP-1. 3. However, concentrations of DA, NE and E, but not 5-HT, in the ventromedial hypothalamic nucleus (VMH) were significantly decreased by GLP-1. 4. These observations suggest that the anorexigenic effect of GLP-1 involves catecholaminergic systems in the VMH in the chick.

Cold-stress induced the modulation of catecholamines, cortisol, immunoglobulin M, and leukocyte phagocytosis in tilapia.

The concentrations of norepinephrine in hypothalamus and norepinephrine and epinephrine in head kidney were significantly decreased in treated tilapia (Oreochromis aureus) during the time course of cold exposure (12 degrees) as compared to the control (25 degrees). The elevation of norepinephrine and epinephrine in plasma was detected earlier than that of cortisol in cold-treated tilapia. Phagocytic activity of leukocytes and the levels of plasma immunoglobulin M (IgM) were depressed in cold-treated tilapia as compared to the control group. Handling stress in the control (25 degrees) also resulted in increased plasma cortisol and decreased plasma IgM levels but not phagocytic activity. In vitro cortisol suppressed leukocyte phagocytosis in a dose (10(-12) to 10(-4) M)-dependent manner. Adrenergic agonist (phenylephrine and isoproterenol) had a significant suppression of phagocytosis only at the highest dose (10(-4) M). No effect on phagocytosis was detected in the treatment with norepinephrine and epinephrine. A combination of cortisol and isoproterenol (0.1 mM) had an additive effect in the suppression of phagocytosis. It is concluded that the cold stress modulated the changes of catecholamines and cortisol and further depressed phagocytic activity and antibody levels in tilapia. Cortisol could play a main and important role in the down-regulation of phagocytic activity. Adrenergic agonists also could interact with cortisol to further suppress immunity in tilapia.

Genetic evidence for noradrenergic control of long-term memory consolidation.

Memory formation involves dynamic interactions among many brain structures and their linking pathways. The noradrenaline (NA) system in the CNS plays an important role in a wide variety of neurological and psychological functions. Alteration in the NA system is implicated in the pathological states of some neuropsychiatric disorders. Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme for the biosynthesis of catecholamines. The regulatory mechanism of the TH reaction is generally considered to play a key role in controlling the catecholaminergic actions. Mice heterozygous for the mutation of the gene encoding TH exhibit the reduced TH activity in tissues. These mice have a moderate reduction in NA accumulation and release in brain regions. The mutant mice exhibit deficits in the water-finding task associated with latent learning performance, suggesting the impairment in memory formation. Spatial learning performance measured by the water maze task is normal in the mutants. However, they display deficits in long-term memory formation of conditioned learning evaluated with three distinct behavioral paradigms, including active avoidance, cued fear conditioning, and conditioned taste aversion, without affecting short-term memory. These memory deficits are restored by the drug-induced stimulation of NA activity at the postconditioning phase. Analysis of the mutant mice indicates that the central NA system is essential for the consolidation process in long-term memory of conditioned learning. The process appears to be implicated in the NA activity in the cerebral cortex and/or amygdaloid complex.

Feeding increases 5-hydroxytryptamine and norepinephrine within the hypothalamus of chicks.

It is thought that hypothalamic 5-hydroxytryptamine (5HT) and norepinephrine (NE) are involved in the regulation of feeding in chicks. The present study was conducted to elucidate changes in the levels of extracellular 5HT and NE in the hypothalamus during feeding of chicks. In order to measure 5HT, NE and 4-hydroxy-3-methoxyphenylglycol (MHPG), which is a major metabolite of NE, we used brain microdialysis and high-pressure liquid chromatography with an electrochemical detector. After collecting samples to determine the basal levels of 5HT, NE and MHPG, food-deprived birds were given access to food. 5HT levels in the medial hypothalamus (MH) and lateral hypothalamus (LH) increased during the first 30 min of feeding, and then returned to basal levels. NE and MHPG in the LH increased during feeding, and remained elevated throughout the experiment. This study supports an idea that hypothalamic monoamines in the chick brain are involved in the regulation of feeding.

Noradrenaline synthesis, release and vesicular transport in the rat brain following subarachnoid haemorrhage.

The present study was designed to estimate the release of noradrenaline, and to evaluate the efficiency of noradrenaline vesicular transport, as indicated from measures of dihydroxyphenylglycol (DHPG), and synthesis in the medulla and hypothalamus following subarachnoid haemorrhage in rats. Subarachnoid haemorrhage was induced by the injection of homologous blood into the cisterna magna (n = 11). Sham operated animals served as controls (n = 11). Three days following subarachnoid haemorrhage, medulla and hypothalamus were dissected and placed in an in vitro superfusion system. Exposure to K(+) (50 mM) for 2 min served as a stimulus for the release of the neurotransmitter noradrenaline, its precursor (dihydroxyphenylalanine [DOPA]) and intraneuronal metabolite, DHPG. Basal noradrenaline overflow from both the medulla and hypothalamus were similar in the two groups of rats but basal DOPA overflow from the medulla was significantly reduced in the subarachnoid haemorrhage animals (0.97 +/- 0.15 vs. 1.97 +/- 0.38 pg/10 min/mg, p < 0.01). Administration of K(+) induced the release of noradrenaline, the response from the medulla in the subarachnoid haemorrhage group being attenuated (p < 0.01) compared with the sham operated animals (174% and 240%, respectively). K(+) induced a similar release of noradrenaline from the hypothalamus in both groups of rats (239% in sham animals and 283% in the subarachnoid haemorrhage group). The overflow of DHPG from both the hypothalamus and medulla was similar in both groups of animals. Our results suggest that the diminution in noradrenaline release from the medulla occurs as a result of a reduction in the rate of noradrenaline synthesis and release.