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)

Methiothepin reduced both median-raphe evoked and exogenous 5-HT depression of single substantia nigra neurones. While this is compatible with a serotonin releasing pathway, additional interactions of methiothepin with exogenous dopamine suggest the need for further pharmacological confirmation.
 ...
PMID:Methiothepin and a 5-HT pathway to rat substantia nigra. 89 76

In 30 patients suffering from vital depression (the syndrome of endogenous depression) a negative correlation was found between the pre-therapeutic post-probenecid CSF 5-HIAA response and the therapeutic response to clomipramine (Anafranil). Clomipramine is a tricyclic antidepressant with a strong potentiating effect on central 5-HT. The following conclusion was drawn: if the cenral 5-HT turnover is diminished in depressions, then correction of this biochemical disturbance leads to alleviation of depressive symptoms. This finding is considered to support the concept of '5-HT-deficient depression'. Five of the 8 clomipramine-resistant patients showed a favourable response to nortriptyline, a NA-potentiating anti-depressant. The pre-therapeutic CSF MHPG concentration in these patients was not related to the therapeutic efficacy of nortriptyline. So, the assumption that these patients have been NA-deficient was not confirmed. However, renal MHPG excretion was not measured and possibly this variable correlates better with cerebral NA metabilism than MHPG in lumbar CSF which is of mainly spinal origin.
 ...
PMID:New evidence of serotonin-deficient depressions. 89 99

The responses of rabbit aortic strips superfused with noradrenaline, adrenaline and 5-HT were studied alone and in combination with ketamine (50 mug/ml). Ketamine caused a slight depression of the isolated aorta but potentiated responses to adrenaline but not to noradrenaline or 5-hydroxytryptamine. Ketamine did not potentiate aortic strips contracted to a stable level by pyrogallol and adrenaline. Experiments carried out with COMT from homogenates of rat liver showed that, in contrast to pyrogallol (10(-5) M), ketamine (10(-3) M) did not inhibit the enzyme. Other experiments with rabbits given 6-hydroxydopamine showed that aortas of these rabbits responded in a similar manner to controls when treated with ketamine and catecholamines. Results obtained with aortas contracted by adrenaline and noradrenaline with ketamine present, followed by oil immersion, showed that ketamine prolonged greatly the relaxation induced by adrenaline and to a lesser extent the relaxation induced by noradrenaline. The results of these studies indicate that ketamine prevented catecholamines from reaching the intracellular site of COMT. In this respect, ketamine can be termed an inhibitor of uptake site 2. If this hypothesis is valid then the action of ketamine on vascular tissue might explain the cardiovascular effects of the drug in man and experimental animals.
 ...
PMID:The actions of ketamine on vascular smooth muscle. 95 82

The effect of electrical stimulation of the median raphe nucleus on the activity of spontaneously firing single neurones in the substantia nigra and mesencephalic reticular formation (MRF) has been investigated in urethane anaesthetized rats. Depression of activity was the predominant effect observed although this was sometimes accompanied by periods of excitation. Some neurones were only excited. The latency of inhibition of substantia nigra neurones was constant whereas that of MRF neurones was more variable. Microiontophoretically applied 5-hydroxy-tryptamine (5-HT) and dopamine (DA) produced mainly inhibition of neuronal activity, but excitation and biphasic effects were also seen. There was a good correlation between the direction of neuronal responses in the substantia nigra to median raphe stimulation and to the effects of 5-HT but not DA. Discrete electrolytic lesions of the median raphe nucleus were followed by a decrease in 5-HT but not GABA concentrations in the substantia nigra. In addition striatal 5-HT, GABA and NA concentrations were unchanged whereas striatal DA was increased. These observations strongly suggest that the substantia nigra receives a direct inhibitory input from the median raphe nucleus and this pathway uses a 5-HT-like neurotransmitter. This pathway probably contributes to the regulation of nigrostriatal dopaminergic transmission.
 ...
PMID:Evidence for the existence of a raphe projection to the substantia nigra in rat. 95 33

D-Amphetamine (Amph) and p-chloroamphetamine (PCA) induced dose-dependent increases in oropharyngeal myocloniform twitch activity (MTA) in rats anesthetized with urethane. In doses of 80-120 mg/kg, gamma-hydroxybutyric acid (GHB) blocked Amph-induced MTA. The blockade was readily surmountable. Pretreatment with reserpine markedly enhanced the myoclonigenic effect of Amph and rendered it insensitive blockade by GHB, 160 mg/kg. PCA and tryptamine also effectively stimulated MTA, but unlike Amph were antagonized by low doses of the serotonin (5-HT) antagonist methysergide. In doses which blocked Amph, GHB failed to antagonize the myoclonigenic effect of PCA. It is concluded that: (a) the actions of Amph and PCA on MTA is less sensitive to GHB blockade than DA-mediated MTA; and (c) the GHB-Amph antagonism may be of a functional nature, i.e. result from a depression of the firing activity of DA neurons produced by GHB. Since reserpinization abolished the GHB effect on Amph-induced MTA, the functional integrity of granular DA binding and releasing mechanisms appears to be a pre-requisite for the antagonism between GHB and Amph.
 ...
PMID:Pharmacological evidence for a selective antidopaminergic action of gamma-hydroxybutyric acid. 97 99

By treating rats with lithium chloride or cocaine hydrochloride, or lithium chloride followed by cocaine hydrochloride, we have shown the antagonistic effects of these drugs on two mechanisms that may be involved in regulating serotonin 5-HT) synthesis in the striate cortex. Lithium chloride (5 to 10 meq/kg/day) stimulates the relative velocity of the active uptake of labelled tryptophan and proportionally enhances the conversion of labelled tryptophan to 5-HT in synaptosomally enriched preparations. With continued administration of lithium chloride, the activity of tryptophan hydroxylase from the median raphe and subsequently in lysed synaptosomal preparations from striate cortex is reduced; the substrate uptake remains enhanced, but the conversion of substrate to transmitter returns to control levels. In contrast, an injection of cocaine hydrochloride inhibits the high affinity uptake of tryptophan, reducing the conversion of the amino acid to 5-HT and resulting in an increase in the biosynthetic enzyme activity. However, administration of cocaine hydrochter three daily lithium chloride injections (10 meq/kg) results in no apparent effects on substrate uptake, conversion, or enzyme activity. We theorize that the effect of lithium was to push two regulatory parameters (the uptake of substrate and the enzyme activity) to their respective functional upper and lower limits, leaving the serotonergic neurons "buffered" against the "usual" effects of the stimulant drug, and offer this neurobiological model for consideration in relation to the clinical effects of lithium in the prophylaxis of both mania and depression in some patients.
 ...
PMID:A neurobiological model for the symmetrical prophylactic action of lithium in bipolar affective disorder. 98 97

Blood platelet serotonin levels were measured in unmedicated 12 manic and 74 depressive patients with 118 normal control subjects employed. Blood platelets were separated by multiple centrifugation in the medium of Na2-EDTA solution, and the loss of serotonin during collecting procedures was about 11%. The mean value of blood platelet serotonin levels in depressed patients was 594 +/- 288 ng/mg platelet protein (+/- S.D.), which was significantly lower than that for normal controls, 780 +/- 253 ng/mg protein (p less than 0.001). Age does not account for the reduction of serotonin levels both in depressed and in normal population. Unipolar and involutional depressed patients exhibited to have the most pronounced reduced levels of serotonin of various subtypes of depression, while bipolar depressed patients, neurotic and chronic characterological depressed patients as well as patients with first-episode depression had the values which were comparable with those in normal controls. Manic patients did not show enhancement but did reduction of serotonin levels, the mean being 580 +/- 152 ng/mg protein, which made a contrast with their clinical manifestations of exhilaration and hyperactivity. Changes in blood platelet serotonin levels were determined before, during and after administration of L-5-HTP with a maintenance dose of 300 mg daily in nine depressed patients. Serotonin levels in all subjects were lifted to normal levels during the L-5-HTP treatment, while clinical symptoms were not improved with the treatment. Reduction of blood platelet serotonin levels in depressed patients may be due to their psychobiological distinction, which involves abnormal biogenic amine metabolism in the brain.
 ...
PMID:Reduction of blood platelet serotonin levels in manic and depressed patients. 102 43

The effect of fornix transection on plasma corticosterone and on midbrain (MID), septum/preoptic (S/POA) or hippocampal (HIP) tryptophan hydroxylase activity (THA) was studied in adult male rats. A mild stress resulted in higher levels of plasma corticosterone in operated as compared to sham-operated rats 6 and 40 h post-transection; however, at 30 days post-operation no difference was found. The response of THA to fornix transection was region-specific. No significant change in the S/POA region was found at any time. THA in the HIP, a terminal area of 5-HT fibers, showed a progressive fall over time to values 80% below normal levels. This result suggests that most of the 5-HT fibers to the HIP had been severed. A 28 h half-life for HIP THA was calculated. THA in the MID, an area known to contain the majority of 5-HT cell bodies with ascending fibers, was significantly reduced compared to sham controls at 6 h, 40 h, and 8 days post-transection. However, at 30 days post-operation no difference was found. The depression in MID THA by its rapid onset, the distance from the fornix transection site, and its return to normal after 30 days, is thought to be due to a transneuronal effect on the serotonin-containing neurons in MID raphe. The fall in MID THA at a time when plasma corticosterone levels are increased in fornix-transected rats may be compared with the situation in normal, stressed and adrenalectomized rats where MID THA andplasma corticosterone levels change in the same direction. The data suggest that the glucocorticoid effects on MID 5-HT containing neurons are mediated transneuronally through the hormone concentrating cells in the HIP.
 ...
PMID:Temporal effects of fornix transection on brain tryptophan hydroxylase activity and plasma corticosterone levels. 102 15

Injections of D,L-5-hydroxytryptophan (D,L-5-HTP) into pigeons and rats working on approach schedules produce a period of behavioral depression that is temporally correlated to increased levels of total serotonin (5-?HT) in the telencephalon and diencephalon. Administration of alpha-methyl-meta-tyrosine (alpha-MMT) also results in depressed responding; however, the temporal correlation is with decreased levels of total 5-HT in brain. Our hypothesis to explain these two apparent opposite biochemical states which result in similar behavioral disruptions is that in both cases more 5-HT is released within certain key serotonergic synapses mediating this behavior. Evidence from subcellular studies supports this concept. tnot only are the levels of 5-HT significantly higher in preparations of nerve endings isolated from the telencephalon and diencephalon of pigeons given injections of D,L-5-HTP, but in vitro studies also show that low concentrations of L-5-HTP significantly increased the release of radioactive 5-HT from serotonergic nerve endings. On the other hand, L-5-HTP in much higher concentrations had no effect on the release of labeled dopamine or norephinephrine. A major metabolite of alpha-MMT, alpha-methyl meta tyramine, also caused a significant increase in the release of labeled 5-?HT from similar preparations of nerve endings. Whereas serotonin appears to be involved in the disruption of approach behavior, another series of studies have indicated that acetylcholine may play a role in excitation during avoidance behavior. Behavioral excitation observed following administration of tetrabenazine 18 hr after iproniazid pretreatment to rats working on shock-avoidance schedules was temporally correlated with lowered levels of acetylcholine in the telencephalon. Pretreatment with 0.8 mg/kg of atropine blocked excitation whereas one-eight of this dose increased the duration. Excitation in these rats was shortened by 50% following bilateral septal lesions, which lowered brain acetylcholine levels. Mechanisms to explain these neurochemical correlates of behavior are discussed.
 ...
PMID:Serotonergic and cholinergic mechanisms during disruption of approach and avoidance behavior. 108 Jan 20

There are indications for a functional deficiency of 5-HT and DA in certain kinds of depression. The question arises if these biochemical disturbances are primary or secondary, whether they contribute to the pathogenesis of the depression or whether they result from it. From research with MA precursors we drew the tentative conclusion that they are presumabely primary and interrelated with the depression in a causal and/or predisposing way.
 ...
PMID:Central monoamine deficiency in depressions: causative of secondary phenomenon? 108 37


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