Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested recently that the therapeutic effects of electroconvulsive therapy (ECT) may be mediated in part through stimulation of pineal melatonin secretion. If melatonin does mediate the antidepressant effects of ECT and depression itself is associated in some patients with reduced melatonin secretion, patients with reduced melatonin secretion could respond less readily to ECT. There is evidence to suggest an inverse relationship between melatonin secretion and the degree of pineal calcification. Specifically, heavy pineal calcifications in animals have been reported to be associated with reduced plasma melatonin levels. In this study, an investigation was conducted to establish more precisely the relationship between the clinical response to ECT in 17 bipolar patients and the degrees of pineal calcification present on CT scan. There was a significant association between ECT nonresponsiveness and the presence of pathologically enlarged pineal calcification (i.e., greater than 1 cm in diameter) (p.01). In addition, there was a significant difference in ECT responsiveness in patients without pineal calcification compared to those with pathologically enlarged pineal calcification (F = 6.10; p = .01, one-way ANOVA). These findings indicate an association between enlarged pineal calcification and ECT nonresponsiveness and suggest that reduced melatonin secretion may be associated with ECT nonresponsiveness. An enlarged pineal calcification could be a useful radiological marker of ECT nonresponsiveness and administration of melatonin precursors (i.e., L-tryptophan; 5-HTP) and its cofactors (i.e., pyridoxine, folate) as well as melatonin-release enhancing agents (i.e., 5-methoxypsoralen) prior to ECT might augment its antidepressant effects in bipolar patients.
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PMID:The relationship between ECT nonresponsiveness and calcification of the pineal gland in bipolar patients. 226 80

Two types of spinal reflex responses, extensor reflex and ventral root potential, were compared physiologically and pharmacologically in acute and chronic spinal cord transected rats. The recovery curve of the extensor reflex, recorded as evoked electromyogram, in chronic spinal rats was strikingly different from that in acute spinal rats. Namely, shortening of the reflex amplitude suppression period (stimulus interval: 20 msec) and appearance of the supernormal period (30-60 msec) were observed in chronic spinal rats. The recovery curves of ventral root potential (monosynaptic reflex) and M wave were almost the same in both preparations. In the frequency depression curve, the amplitude of the extensor reflex in chronic spinal rats was higher at high frequency stimulation than that in acute spinal rats. 5-Hydroxytryptophan, 5-methoxy-N,N-dimethyltryptamine and quipazine enhanced the extensor reflex in chronic spinal rats with a potency of 200-400, 8 and 4 times stronger than that in acute spinal rats, respectively. These drugs did not show consistent effects on the monosynaptic reflex of ventral root potential in chronic spinal rats. These results strongly suggest that the spinal interneurons where descending serotonergic fibers terminate become supersensitive and functionally modified in chronic spinal rats. It is speculated that the supersensitivity of these interneurons may play an important role in spasticity.
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PMID:Functional change in the rat spinal cord by chronic spinal transection and possible roles of monoamine neurons. 387 2

Brain perfusion experiments of conscious rats engaged in operant behavior and administered fluoxetine or LSD, with or without prior injection of 5-HTP, indicate there is probably more than one functional pool of 5-HT in the CNS. Furthermore, the fact that prior loading with the precursor is necessary before unmasking an effect of LSD suggests the LSD-sensitive pool is newly synthesized and represents only a small fraction of total CNS serotonin. Separating the effects of LSD's behavioral action into pausing (disruption) and depressed responding rate, with or without pausing, enabled us to demonstrate blockade of the disruption by methysergide without blockade of the decreased responding rate. Mianserin blocks both effects of LSD's action. We suggest that behavioral effects of low doses of LSD are due to sympathetic arousal and may offer a model for agitated depression and/or anxiety and that drugs of the mianserin-type may prove useful for treating some forms of anxiety, as well as depression.
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PMID:Studies on the specificity of neurochemical and behavioral effects of LSD-25. 395 24

1. Spontaneous and reflex activity was recorded from renal and splanchnic nerves and thoracic white rami during discrete electrical stimulation within the medulla oblongata of anaesthetized cats.2. Inhibition or excitation of spontaneous sympathetic nerve activity was obtained from several medullary regions.3. The long-circuited reflex elicited in renal nerves and the spinally mediated reflex discharge produced in white rami by single shock stimulation of intercostal nerves were inhibited by stimulation within the sympatho-inhibitory areas of the medulla.4. Activation of spontaneous sympathetic nerve activity or inhibition of spontaneous and reflex sympathetic nerve activity was obtained during electrical stimulation within the lateral funiculi of the cervical spinal cord in unanaesthetized decerebrate cats, spinalized at C1.5. There was a correlation between the position of some sympatho-inhibitory regions of the medulla and spinal cord and the position of the cell bodies and axons of descending monoamine-containing neurones.6. Intravenous administration of the precursor of noradrenaline, L-DOPA, to unanaesthetized decerebrate cats, spinalized at C1, was followed by a depression of spontaneous activity in renal nerves and reflex responses elicited in renal nerves and white rami.7. Similarly the precursor of 5-hydroxytryptamine, 5-HTP, caused a depression of reflex activity elicited in renal nerves and white rami, but had no effect on spontaneous renal nerve activity.8. It is suggested that there exist both noradrenergic and tryptaminergic pathways which descend to the spinal cord from the medulla and which are inhibitory to sympathetic outflow.
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PMID:The influence of bulbospinal monoaminergic pathways on sympathetic nerve activity. 454 38

Using substrate induction as a tool, we attempted to determine the role of tryptophan pyrrolase in the response to endotoxin in mice. Previous results have shown that the administration of the ld(50) of endotoxin lowers tryptophan pyrrolase activity. alpha-Methyltryptophan was found to maintain tryptophan pyrrolase activity above control levels in endotoxin-poisoned mice without increasing survival. 5-Hydroxytryptophan, by contrast, lowered tryptophan pyrrolase activity but did not sensitize mice to endotoxin. These results suggest that tryptophan pyrrolase per se does not play a unique role in survival of mice poisoned with endotoxin. This enzyme, however, may reflect the fate of other liver enzymes inducible by adrenocorticoids. In mice given concurrent injections of tryptophan and endotoxin, tryptophan pyrrolase activity was elevated to a level intermediate between that of normal mice and that of mice given tryptophan alone. The mice injected with tryptophan and endotoxin also had about the same mortality as mice given endotoxin alone. Mice treated with tryptophan 4 hr after endotoxin, at a time when the substrate did not fully elevate tryptophan pyrrolase activity, died convulsively and in larger numbers than those given endotoxin alone. This effect was reversed by prior treatment with cyproheptadine, an antiserotonin drug. These results indicate that the depression of tryptophan pyrrolase activity previously observed in vitro after injection of endotoxin reflects an actual decrease in the in vivo activity of the enzyme.
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PMID:Role of tryptophan pyrrolase in endotoxin poisoning. 486 11

The effects of acute and chronic lithium chloride administration on synaptic transmission between bulbospinal norepinephrine (NE) or 5-hydroxy-tryptamine (5-HT) pathways and sympathetic preganglionic neurons were tested in unanesthetized, spinal cats. Discharges recorded from sympathetic preganglionic white rami were evoked by stimulation of spinal reflex pathways or descending excitatory pathways in the cervical spinal cord. Acute lithium administration (2 meq/kg) produced insignificant depression of the reflex pathway but markedly depressed transmission through the intraspinal pathway, an effect that was prevented by depletion or blockage of 5-HT. These observations and the failure of lithium to alter the typical effects of L-dopa on both pathways indicate that lithium does not affect transmission through the excitatory NE pathway. L-Tryptophan (1,0 mg/kg) alone produced little or no depression of either pathway, but 3--4 hr after lithium, this dose of L-tryptophan gradually depressed transmission through both pathways by about 20%. After chronic lithium pretreatment (1 meq/kg twice a day for 3 days), L-tryptophan rapidly depressed transmission through spinal reflex and intraspinal pathways by 40% and 50% respectively. Chronic lithium pretreatment also more than doubled the depression of transmission through both pathways produced by 30 mg/kg of 5-HTP. The average of plasma lithium levels 8--10 hr after the last chronic dose was 1.5 meq/liter. These results support the proposal that lithium increases the uptake of L-tryptophan and 5-HTP by central 5-HT terminals and thereby enhances 5-HT synthesis which is reflected in increased transmission at central 5-HT synapses.
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PMID:Lithium enhancement of central 5-HT transmission induced by 5-HT precursors. 624 11

For a long time antidepressants have been considered to act via enhancement of central monoaminergic activity (due to reuptake or MAO inhibition). An alternative hypothesis holds that their action is based on down-regulation of monoaminergic activity (due to decrease in density or sensitivity of certain receptor populations). In this paper the likelihood of both hypotheses is discussed and the conclusion reached that the first one is the most plausible. The following arguments are discussed: (1) the 5-HT precursor 5-HTP, which is transformed to 5-HT in the brain, has antidepressant properties; (2) there are indications that the same holds true for tyrosine, a catecholamine precursor transformed in the brain to DA and NA; and (3) evidence was found that the effects of 5-HTP in depression are potentiated by tyrosine. Since activation rather than suppression of monoaminergic activity seems to be linked to antidepressant activity, it seems likely that the signs of decreased monoamine metabolism that have been demonstrated in certain types of depression are the expression of a primary metabolic deficit rather than a phenomenon secondary to receptor hypersensitivity. Further clinical studies of 5-HT/CA precursor combinations in depression are justified.
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PMID:In search of the mode of action of antidepressants. 5-HTP/tyrosine mixtures in depressions. 630 61

For a long time, antidepressants have been considered to act via enhancement of central MA-ergic activity (due to reuptake or MAO inhibition). An alternative hypothesis holds that their action is based on down-regulation of MA-ergic activity (due to decrease in density or sensitivity of certain receptor populations). In this chapter I have discussed the likelihood of both hypotheses and have reached the conclusion that the first one is the more plausible. I have discussed the following arguments: The 5-HT precursor 5-HTP, which is transformed to 5-HT in the brain, has antidepressant properties. There are indications that the same holds true for tyrosine, a CA precursor transformed in the brain to DA and NE. I found evidence that the 5-HTP effects in depression are potentiated by tyrosine. Since activation rather than suppression of MA-ergic activity seems to be linked to antidepressant activity, it seems likely that the signs of decreased MA metabolism that has been demonstrated in certain types of depression are the expression of a primary metabolic deficit rather than a phenomenon secondary to receptor hyper-sensitivity. Further clinical studies of 5-HT/CA precursor combinations in depression are justified.
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PMID:In search of the mode of action of antidepressants: 5-HTP/tyrosine mixtures in depression. 638 Feb 26

Parasympathetic preganglionic discharges recorded from pelvic nerves in spinal cats were evoked by single-pulse stimulation of sacral afferent fibers of descending excitatory pathways in the thoracic spinal cord. Evoked responses were analyzed on-line by signal averaging. Discharges evoked by either pathway were increased in size by 2-10 times by coadministration of both picrotoxin and strychnine, but not by either drug alone. The combination also markedly enhanced evoked increases in bladder pressure. Strychnine was also effective with bicuculline and in cats depleted of central GABA stores by semicarbazide. The monoamine precursors, 5-HTP and L-dopa, only depressed evoked discharges in both untreated and convulsant-treated animals; this depression was enhanced by tricyclic antidepressants. The results indicate that sacral parasympathetic preganglionic neurons are controlled by an unusual type of strong, local tonic inhibition which is mediated by both GABA and glycine. Both amino acid transmitters must be blocked to unmask this inhibition. Interruption of supraspinal control of this local inhibition may account in part for loss of bladder function following spinal injuries. The 5-HT and NE bulbospinal pathways that terminate near the preganglionic neurons also appear to be inhibitory. Enhancement of this inhibitory monoaminergic transmission by tricyclic antidepressants may contribute to the efficacy of these drugs in treating nocturnal enuresis.
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PMID:Amino acid and monoamine inhibition of sacral parasympathetic preganglionic neurons. 697 82

The effects of clonidine HCI were compared with those of 5-HTP on transmission through two spinal sympathetic pathways, segmental spinal reflex pathways and descending intraspinal excitatory pathways, in unanesthetized spinal cats. Evoked sympathetic discharges were recorded from upper thoracic preganglionic rami. Clonidine (5-50 microgram/kg) produced a parallel, dose-dependent depression of transmission through each pathway. The intraspinal pathway was five time more sensitive than the spinal reflex pathway (ED50's, 6 and 30 microgram/kg), and the spinal reflex pathway could not be depressed by more than 60% even by higher doses. In contrast, 5-HTP was more effective in depressing the spinal reflex than the intraspinal pathway (ED50's 32 and 44 mg/kg), and both pathways could be depressed completely. Small doses of tolazoline or yohimbine rapidly antagonized the effects of clonidine but not 5-HTP. Clonidine and 5-HTP appear to depress the excitability of sympathetic preganglionic neurons by activating alpha2- and 5-HT receptors, respectively. Each mechanism may contribute independently to regulation of the sympathetic outflow.
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PMID:Contrasting effects of clonidine and 5-hydroxytryptophan on spinal sympathetic pathways. 697 34


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