UMLS:C0011570 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

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.
...
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)
...
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.
...
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.
...
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.
...
PMID:Focal traumatic brain injury causes widespread reductions in rat brain norepinephrine turnover from 6 to 24 h. 782 6

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.
...
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)
...
PMID:Development of neurochemical and behavioral sensitivity to ethanol in long-sleep and short-sleep mice. 851 37

It is well documented that dehydroepiandrosterone (DHEA), an adrenal androgen, is converted into potent androgens and/or estrogens in peripheral tissues. Since sex steroids are involved in the regulation of prolactin (PRL) secretion, we have studied the effect of DHEA administration on PRL mRNA levels in both adult male and female rats. Since tuberoinfundibular dopaminergic (TIDA) neurons are involved in the negative regulation of PRL, we have also evaluated the effects of DHEA on the genetic expression of tyrosine hydroxylase (TH), the limiting enzyme in catecholamine biosynthesis in TIDA neurons. Sham-operated and castrated animals of both sexes received during 2 days DHEA at the dose of 6 mg/kg/day, starting on the first day after castration. PRL and TH mRNA levels were measured by quantitative in situ hybridization. In the male rat, orchiectomy performed 3 days earlier did not modify PRL mRNA levels. DHEA administration increased the hybridization signal in both sham-operated and orchiectomized animals. In the female, ovariectomy decreased PRL mRNA levels and, as observed in the male, DHEA treatment induced an increase in the hybridization signal in both control and ovariectomized rats. In TIDA neurons, castration increased TH mRNA levels as evaluated by number of grains over labelled neurons and the number of TH-labelled cells per section in both male and female animals. In both sham-operated male rats and orchiectomized animals, DHEA decreased the hybridization signal. In the female, DHEA administration completely prevented the increase in TH mRNA levels due to ovariectomy. In sham-operated female rats, the treatment had no effect. These data clearly indicate that in both male and female rats DHEA exerts an estrogenic influence on both PRL and TH gene expression. Although these in vivo experiments do not allow to establish whether the stimulation of PRL gene expression is due to an action of the steroid on the pituitary or at the hypothalamic level or alternatively at both sites, it is likely that one of the mechanisms of action of DHEA might be related to a decrease in dopamine release following a depression of TIDA neuron activity.
...
PMID:Effects of dehydroepiandrosterone (DHEA) on pituitary prolactin and arcuate nucleus neuron tyrosine hydroxylase mRNA levels in the rat. 870 32

Antidepressant drugs have in common a delayed onset of clinical efficacy. In rats, long-term, daily administration of four different types of clinically effective antidepressant drugs results in decreased corticotropin releasing hormone (CRH) mRNA expression levels in the hypothalamic paraventricular nucleus (PVN). Because a subpopulation of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (Arc) projects to the PVN, we measured NPY and POMC mRNA expression in the Arc using in situ hybridization histochemistry at several time points following daily administration of four different antidepressant drugs. After 14 and 56 days of imipramine treatment, Arc NPY mRNA levels are decreased to 85% and 75% of control levels, but are unchanged compared to control after one or five days of treatment. Arc POMC mRNA levels are unchanged compared to controls at 1, 5, 14, or 56 days following imipramine treatment. Unlike after imipramine, Arc NPY and POMC mRNA levels are increased significantly to 134-172% of control following 56-day treatment with the antidepressant drugs fluoxetine, phenelzine, or idazoxan. The divergent effects of imipramine vs the other 3 antidepressant drugs on Arc NPY mRNA expression are similar to the pattern of changes in tyrosine hydroxylase (TH) mRNA expression levels in the locus coeruleus (LC) using the same experimental paradigm, but are different from the unidirectional depressive effects of all four drugs on CRH mRNA expression in the PVN. Thus, the Arc NPY and LC noradrenergic systems may act coordinately in mediating antidepressant effects. The present data are consistent with the delayed onset of clinical efficacy for antidepressant drugs, and suggest that Arc NPY and POMC neurotransmitter systems play a role in the pathophysiology of depression.
...
PMID:Effects of long-term treatment with antidepressant drugs on proopiomelanocortin and neuropeptide Y mRNA expression in the hypothalamic arcuate nucleus of rats. 873 33

Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain.
...
PMID:The interpeduncular nucleus regulates nicotine's effects on free-field activity. 874 44

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>