UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study was made of the central effects of tuftsin (Thr-Lys-Pro-Arg) and its analogs (Leu1-tuftsin, D-Arg4-tuftsin) on the dopamine-dependent behavior and tyrosine hydroxylase (TH) activity. It was shown that the absence of direct effect of tuftsin and Leu1-tuftsin on postsynaptic dopaminergic receptors, revealed in experimental rotational behavior, correlates with a decrease in TH activity in the rat hypothalamus and striatum. Depression of the rotational behavior and increased activity of TH under the effect of D-Arg4-tuftsin suggest that this analog can modulate postsynaptic dopaminergic receptors by the antagonism type.
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PMID:[Analysis of the neurochemical mechanisms of the psychotropic action of tuftsin and its analogs]. 612 53

The effects of treatment with and withdrawal from lithium (Li, 2 mmol/kg) on central catecholamine systems in rat brain were investigated. Synthetic parameters were found to be unchanged after treatment, but abrupt withdrawal resulted in enhanced activity of tyrosine hydroxylase. Noradrenaline levels in most brain regions examined were depressed following both short- and long-term Li administration, with a further decrease in content in the pons but enhanced cortical levels on withdrawal. Li administration resulted in elevated 3,4-dihydroxyphenylacetic acid levels, whereas withdrawal caused an enhancement of homovanillic acid content and depression of 3-methoxy-4-hydroxyphenyl glycol levels. It appears that the changes in central catecholamine systems are qualitatively the same following both short- and long-term Li treatment, as are the consequences of abrupt Li withdrawal. It is suggested that Li administration results in a disruption of catecholamine storage processes, while withdrawal from Li does not result in a simple return towards normal states.
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PMID:Comparison of the changes in central catecholamine systems following short- and long-term lithium treatment and the consequences of lithium withdrawal. 615 62

Rats treated with iprindole (IPR) (10 mg/kg, i.p.) were given a single dose (15 mg/kg, i.p.) of amphetamine (AMP). Marked decreases in the activity of tryptophan hydroxylase (TPH) were observed in both the cerebral cortex and neostriatum after 6 hr, with maximum depression observed at 24 hr. Enzyme activity had returned to control levels in neostriatum after 3 days and in cerebral cortex after 7 days. Levels of serotonin (5-HT) in both the cerebral cortex and neostriatum were significantly lowered at 24 hr but had recovered by 72 hr. Levels of tryptophan (TRP) in the cortex were significantly elevated after 6 hr, recovering by 24 hr. In the neostriatum, the activity of tyrosine hydroxylase (TH) was significantly depressed by 24 hr and remained so for 7 days. Concentrations of dopamine (DA) were decreased at all times examined. This study clarifies the differences previously observed in the response of the serotonergic system to amphetamine or methamphetamine (METH) in iprindole-treated rats.
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PMID:The effects of a single dose of amphetamine and iprindole on the serotonergic system of the rat brain. 620 34

The preovulatory surge of luteinizing hormone reaches a maximum at 18.00 h on the day of pro-oestrus in female rats maintained with regular lighting from 06.00 to 20.00 h. This surge is initiated by a discharge of luteinizing hormone-releasing hormone into hypophysial portal blood. In this study, drugs which affect catecholamine-mediated neurotransmission were administered on the day of pro-oestrus and the effects on serum concentrations of luteinizing hormone and on subsequent ovulation were observed. alpha-Methyl-p-tyrosine, diethyldithiocarbamate and SKF 64139 inhibit catecholamine synthesis at the level of tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase, respectively. Although alpha-methyl-p-tyrosine suppressed ovulation, it had a negligible effect on the incidence of the preovulatory surge. In contrast, the various treatments with diethyldithiocarbamate and SKF 64139 resulted in a minimal occurrence of the 18.00 h surge; at relatively low doses, however, these drugs frequently elicited a surge at 22.00 or 24.00 h which invariably resulted in ovulation. The failure of the surge after diethyldithiocarbamate or SKF 64139 was not associated with a loss of pituitary sensitivity to luteinizing hormone-releasing hormone. In terms of the hypothalamic concentration of dopamine, noradrenaline, adrenaline and 5-hydroxytryptamine at 18.00 h on pro-oestrus, the only common effect of diethyldithiocarbamate and SKF 64139, given in a dose which blocks the surge, was a severe depletion of adrenaline; alpha-methyl-p-tyrosine failed to produce this effect despite inducing a marked depression of dopamine and a moderate loss of noradrenaline. Neither the increase in hypothalamic dopamine after diethyldithiocarbamate, nor the alpha 2 receptor blocking properties of SKF 64139 appear to be relevant in this context since injections of L-dopa or piperoxane, an alpha 2 receptor antagonist, were without effect on the surge or ovulation. The failure of the surge after prazosin, an alpha 1 receptor antagonist, indicates that the function of adrenaline may be mediated postsynaptically by alpha 1 receptors. Clonidine, an alpha 2 receptor agonist which reduces the turnover rate of hypothalamic adrenaline, had effects of the surge and ovulation which were comparable to those of diethyldithiocarbamate and SKF 64139, the relatively low doses causing some of the surges to occur at 24.00 instead of 18.00 h and higher doses suppressing the surge at both times and thus preventing ovulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of manipulating catecholamines on the incidence of the preovulatory surge of of luteinizing hormone and ovulation in the rat: evidence for a necessary involvement of hypothalamic adrenaline in the normal or 'midnight' surge. 635 42

A neuropharmacologic approach was utilized to investigate the catecholaminergic influence on the hypothalamic regulation of growth hormone (GH) secretion in young (6-week-old) male domestic fowl. The selective inhibition of norepinephrine (NE) and epinephrine (E) synthesis or activity by diethyldithiocarbamate (DDC), FLA63 (dopamine-beta-hydroxylase inhibitors), phenoxybenzamine (alpha 1 receptor blocker), and yohimbine (alpha 1 and alpha 2 receptor antagonist) was associated with a decline in circulating GH levels. Similarly inhibition of NE reuptake by imipramine or desmethylimipramine were followed by reduced GH secretion. In the presence of alpha-methyl-p-tyrosine (alpha Mpt, a tyrosine hydroxylase inhibitor), the administration of phenylephrine (alpha 1 agonist) was followed by increased plasma concentrations of GH. However, alone, it was without effect. Similarly plasma concentrations of GH were elevated by dihydroxyphenylserine (DOPS, a precursor of NE/E) in chicks pretreated with DDC or carbidopa. These data are consistent with the stimulatory hypothalamic control of GH involving NE/E which exert their effects via alpha (probably alpha 1) postsynaptic stimulatory receptors. Evidence that it is E rather than NE, which is the catecholamine involved or the hypothalamic control of GH, comes from the decrease in plasma GH concentration following the inhibition of central E synthesis by SKF64139 (an inhibitor of phenylethanolamine-N-methyltransferase). Some evidence for a limited inhibitory dopaminergic system was found. Inhibition of dopamine (DA) synthesis by alpha Mpt produced significant elevations in plasma GH concentration. In addition, apomorphine (DA agonist) consistently depressed GH release. However, blockade of DA receptors by pimozide had either no effect on plasma GH concentrations or at a very high dose decreased plasma GH concentrations. NE/E also appear to have a depressive effect on plasma concentrations of GH in young chicks, probably via a peripheral site of action. Plasma concentrations of GH were reduced by the peripheral administration of NE, which might be expected not to cross the blood-brain-barrier (BBB), alpha 1/alpha 2 agonists clonidine and p-amino clonidine (which does not cross BBB), NE/E precursors L-DOPA and DOPS, and the beta agonist, isoproterenol. Furthermore, the depression of peripheral E synthesis (by SKF29661 which inhibits phenylethanolamine-N-methyltransferase) elevated the plasma concentration of GH.
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PMID:Catecholamine involvement in the control of growth hormone secretion in the domestic fowl. 673 52

Heart failure is associated with a reduction in tissue norepinephrine concentration, catecholamine fluorescence, and tyrosine hydroxylase activity. We hypothesized that this attrition of sympathetic nerve function might also be associated with a reduction in the ability of the neuronal membrane to sequester catecholamines. Since the heart does not release epinephrine, the cardiac extraction of epinephrine should be an index of the membrane uptake system. In 12 patients with documented left ventricular failure (pulmonary edema) secondary to mechanical overload and in 10 patients with no history of heart failure, we measured simultaneous plasma catecholamine concentrations in the aorta, coronary sinus, and femoral vein. The aortocoronary sinus extraction of epinephrine was 43 +/- 17% in the group with no evidence of heart failure but 0 +/- 14% in the group with failure. Net norepinephrine outflow (release minus extraction) was significantly higher in the group with failure, possibly because of reduced extraction. There was neither a reduction in the ability of the lower limb to extract epinephrine nor an increased norepinephrine outflow from the limb. These findings suggest that the sympathetic neuronal membrane uptake system is also depressed in the failing heart and that if the mechanism of catecholamine sequestration in the heart is related to that in the lower limb, the ablation of sympathetic nerve function is specific to the heart and is not a result of a generalized depression of the peripheral sympathetic nervous system.
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PMID:Reduced aortocoronary sinus extraction of epinephrine in patients with left ventricular failure secondary to long-term pressure or volume overload. 686 2

The effect of right sensorimotor traumatic brain injury (TBI) in male Sprague-Dawley rats on brain norepinephrine (NE) turnover was assessed by measuring the decline of endogenous NE levels following tyrosine hydroxylase inhibition produced with alpha-methyl-p-tyrosine. Right sensorimotor cortex contusions were produced by a pneumatically driven piston which depressed the dural surface by 2 mm at 3.2 m/s. TBI rats were compared to uninjured, anesthetized controls at 6 h and 24 h after surgery. While NE turnover was not affected at the lesion site at 6 h after TBI, it was either abolished or decreased by 33-75% bilaterally in the hypothalamus and in the cerebral cortex surrounding and rostral to the lesion site. In the cortex caudal to the lesion site, NE turnover was completely abolished. NE turnover in cerebral cortex opposite the lesion site and in the contralateral cerebellum was decreased by 51 and 43%, respectively, at 6 h. At 24 h, NE turnover was either abolished or decreased bilaterally by 45-92% in all cortical areas, in the hypothalamus, cerebellum, locus coeruleus and medulla. Thus, right sensorimotor cortex contusion causes a marked, early and widespread depression of brain NE turnover. Since amphetamine increases NE turnover, this may explain the dramatic improvement in behavioral deficits which occurs following amphetamine administration at 24 h after such lesions.
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PMID:Focal traumatic brain injury causes widespread reductions in rat brain norepinephrine turnover from 6 to 24 h. 782 6

Neuropeptide Y (NPY) is found to be costored with norepinephrine (NE) in vesicles of the nerve terminals. Tyrosine hydroxylase (TH), the synthetic enzyme of NE, has been mentioned to be a rate-limiting step. In an attempt to understand the effect of NPY on TH activities, an in vitro assay is carried out using chromatographic analysis of 3,4-dihydroxyphenylalanine (DOPA) formation from tyrosine. NPY (40-120 pmol/ml) produced a dose-dependent depression of DOPA formation catalysed by the adrenal TH of rats. Lineweaver-Burk plot (Km = 156 microM, Vmax = 1.05 nmol/h/mg protein) showed a non-competitive inhibition in NPY (80 pmol/ml, IC50)-treated samples. Moreover, failure of denatured NPY even at maximum concentration to influence the TH activities suggested the essential of nature form for NPY. Participation of pterine cofactor seems also negligible, because increase of 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine did not overcome the effect of NPY. These results indicate that NPY has the ability to inhibit the catalytic action of TH in the adrenal gland of rats.
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PMID:Inhibitory effect of neuropeptide Y (NPY) on the in vitro activity of tyrosine hydroxylase. 790 29

Unipolar depression, alcoholism and suicide have become more common over the past decades. Genetic studies have attempted to link (bipolar) affective disorder to the short arm of chromosome 11 (where the loci for insulin, insulin growth factor (IGF), tyrosine hydroxylase (TH) and h-ras-oncogene are located) but these have failed. Since TH and the insulin receptor require phosphorylation by protein kinases, then a defect of the h-ras-oncogene or its products (p21) could disorder both these systems and compromise catecholaminergic transmission in neurones and energy flow in glial cells. This could lead not only to a predisposition to depression ('trait markers') but to neurotoxic damage, predisposed by inadequate cytosol Mg2+ levels of hypometabolism. Tyrosine, tryptophan and phenylalanine hydroxylases all require tetrahydrobiopterin (BH4) which allosterically regulates its own activity as well as that of these enzymes. Anything which impairs this cofactor could lead to overt depression in predisposed individuals, and the heterocyclic amines are being increasingly implicated. These substances are derived from fried and broiled meats, azo food dyes, soft drinks and hard candies, but particularly from cigarette and petroleum fumes. The heterocyclic amines can inhibit aromatic-l-amino-acid-decarboxylase (AADC) as well as the hydroxylases reversibly, but BH4 is inhibited noncompetitively. Thus, susceptible individuals (those with inherited defective protein kinase phosphorylation) might be 'tipped over' by chronic exposure to these neurotoxins. The rising incidence of unipolar depression-associated morbidity could be significantly linked to increasing levels of heterocyclic amines in the developed nations.
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PMID:The 'cerebral diabetes' paradigm for unipolar depression. 814 51

The postnatal development of certain neurochemical correlates of CNS ethanol sensitivity was examined in the long-sleep (LS) and short-sleep (SS) mice. The differences in sensitivity to the motor-incoordinating and hypothermic effects of ethanol emerged during the second and third weeks of life. Prior studies have shown the sleep time differences between LS and SS mice became significant at 8-10 days of age whereas the present results established that the differences in ethanol-induced hypothermia became prominent at 12-16 days of age. Previous results from our laboratory suggested that the greater CNS ethanol behavioral sensitivity (sleep time and hypothermia) of LS mice is related to the greater ethanol-induced depression of brain monoamine synthesis in the LS line. The timing of the developmental changes in neurochemical ethanol sensitivity in LS and SS mice was found to parallel that found in the development of behavioral ethanol sensitivity as follows. Ethanol-induced decreases in in vivo tyrosine hydroxylase activity in the cerebellum, hypothalamus, and brain stem did not differ between LS and SS mice at postnatal day 8, but became substantially greater in LS mice between postnatal days 8 and 12, coincident with the appearance of the greater sleep times of LS mice. Likewise, ethanol-induced decreases in in vivo tryptophan hydroxylase activity in the dorsal raphe and hypothalamus, which were similar in LS and SS mice at postnatal days 8 and 12, became significantly greater in LS mice by postnatal day 16, the age at which their increased sensitivity to ethanol-induced hypothermia appeared.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of neurochemical and behavioral sensitivity to ethanol in long-sleep and short-sleep mice. 851 37

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