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)

Changes of serotonin2 (5HT2) receptors have been described in depression, and long-term antidepressant treatment has been shown to decrease the number of 5HT2 receptors. In this study, single photon emission computed tomography (SPECT), with 2-123I-ketanserin as a ligand, was used to investigate 5HT2 receptors in vivo in the brain of depressed patients and normal volunteers. A higher uptake of the tracer was observed in the parietal cortex of the patients, and there was a right greater than left asymmetry in the infero-frontal region of the depressed subjects and not in that of the control subjects. These findings could indicate changes in 5HT2 receptors in major depression.
 ...
PMID:SPECT imaging of serotonin2 receptors in depression. 129 40

Ablation of the olfactory bulbs in mice C57Bl/6j was accompanied by motor and orienting-exploratory activity augmentation in the "open field" test and deterioration of the learning ability to active and passive avoidance. The most expressed behavioural changes developed in four weeks after the surgery. Chronic administration of antidepressants (amitriptyline, 20 mg/kg; trazodone, 20 mg/kg; imipramine, 10 mg/kg; intraperitoneally) normalized behaviour of bulbectomized animals, trazodone being the most effective. In the biochemical studies the brainstem serotonin level was found to be decreased and the density of 5HT2-receptors in the cerebral cortex increased in bulbectomized mice. Only trazodone was able to correct the biochemical indices. The state of the bulbectomized mice is supposed to serve a model of a depression with hypo-function of serotonergic system of the brain.
 ...
PMID:[The behavioral and biochemical sequelae of the removal of the olfactory bulbs in C57Bl/6j mice]. 133 99

Ondansetron, a specific 5-hydroxytryptamine3 (5-HT3)-blocker, injected s.c. (0.038, 0.075, 0.15 or 0.3 mg/kg) every 12 h with the fourth dose given 0.5 h before restraint at 4 degrees C (stress) or oral administration (p.o.) of 1 ml 80% ethanol, dose-dependently prevented gastric mucosal damage in female Sprague-Dawley rats (160-180 g); the animals were killed 2 or 1 h after stress or ethanol p.o., respectively. A similar pretreatment regimen with cyproheptadine (0.1, 0.25 or 0.5 mg/kg) or ketanserin (15, 30, or 75 micrograms/kg), both being 5HT2-receptor antagonists, also dose-dependently lowered the severity of stress- or ethanol-induced mucosal lesions. Only the higher doses of phenobarbitone (25 or 50 mg/kg given s.c. in a single dose 0.5 h beforehand) inhibited stress-induced gastric ulcers; however, even the lowest non-antinuclear dose (12.5 mg/kg), effectively produced CNS depression. These preliminary findings suggest that 5HT3-receptor blockade not only can antagonise stress- or ethanol-evoked gastric mucosal damage, but also may act through a peripheral mechanism.
 ...
PMID:5-Hydroxytryptamine3-receptor blockade protects against gastric mucosal damage in rats. 134 85

1. Studies of the biochemical mechanism of action of antidepressant drugs show that virtually all drugs, regardless of acute biochemical effects, result in the down regulation of CNS beta-1 adrenergic, serotonin-2 (5HT2), and perhaps 5HT1A receptors in rats in a time course which parallels the onset of antidepressant action in patients with major depressive disorder. 2. Recently, neuroendocrine techniques have been described which allow the study of 5HT receptor subtypes in man. These include fenfluramine-induced changes in ACTH, cortisol and prolactin secretion (perhaps for 5HT2 receptors) and ipsapirone-induced changes in ACTH and cortisol (for 5HT1A receptors). 3. Depressed subjects treated with antidepressants down regulate these markers of both 5HT2 and 5HT1A receptors in a time course consistent with their recovery from depression. 4. Studies in progress are attempting to demonstrate links between these receptor changes and clinical antidepressant responses.
 ...
PMID:Neuroendocrine markers of serotonin responsivity in depression. 149 23

Experiment 1 showed that the reduction of intake produced by 5 or 10 mg/kg fluoxetine in rats eating either a solid or a liquid meal was partially antagonised by 1 mg/kg of the 5HT1/5HT2 antagonist metergoline but not by 1 mg/kg of the 5HT2 antagonist ketanserin. Experiment 2 examined the meal patterning of rats given 5 mg/kg fluoxetine and 1 mg/kg metergoline. Fluoxetine alone increased the latency to feed, reduced meal size and shifted the inter-pellet interval (IPI) distribution to the right. Metergoline alone had little immediate effect on food intake or other feeding parameters but partially reversed the reduction of food intake produced by fluoxetine. There was a complete reversal of the increased latency to feed and a partial reversal of the depression of meal size. However, the rightward shift of the IPI distribution caused by fluoxetine, which indicated a depression of feeding rate, was more pronounced after combined treatment. We conclude that fluoxetine reduces food intake by enhancing satiety through a serotonergic dependent mechanism but reduces feeding rate through a separate mechanism, whose neurochemical basis remains to be established.
 ...
PMID:Partial reversal of fluoxetine anorexia by the 5-HT antagonist metergoline. 161 37

The 5HT-induced shape change (5HT-SC) of blood platelets, which had been suggested to reflect the 5HT2 receptor-mediated function of the central nervous system (CNS), was examined in patients with depression before or after antidepressant therapy. The degree of 5HT-SC did not differ between patients before treatment (n = 17) and healthy controls (n = 26). In patients after treatment (n = 12), in whom depression had been improved but drug therapy was continued, 5HT-SC in a concentration of 10(-5) M 5HT was observed more potently than that in healthy controls or untreated patients (p less than 0.05 and p less than 0.05, respectively). In 4 patients in whom 5HT-SC was measured before and after mianserin treatment, 5HT-SC increased after the treatment. These results suggest that the 5HT2 receptor-mediated function in the CNS may not be damaged in patients with depression, and that the 5HT2 receptor-mediated function in the CNS may be enhanced by antidepressants.
 ...
PMID:5HT2 receptor-mediated function in depressed patients: investigation by measuring 5HT-induced shape change of blood platelets. 163 6

The potentiation of fluoxetine by buspirone is described in three cases of treatment-resistant depression. All three patients improved markedly with very few side-effects from the medication. The possibility of synergy between drugs that affect serotonin reuptake inhibition, 5HT1A receptors and 5HT2 receptors is discussed.
 ...
PMID:Fluoxetine potentiation by buspirone: three case histories. 179 May 22

5HT has been implicated in mechanisms of anxiety and depression for many years but the evidence is contradictory. Perhaps one error has been to think of 5HT as a unitary system when in reality it is highly differentiated. There has been an explosive increase in knowledge about different 5HT receptor subtypes and it has long been known that there are different anatomical subsystems. Evidence will be summarised that the different systems subserve different psychological functions and that dysfunction in the different systems results in depression, anxiety, panic and OCD in an understandable way. Much evidence is compatible with the idea that 5HT systems reduce the impact of impending or actual aversive events. Anticipation of an aversive event is associated with anxiety and this motivates avoidance behaviour--a normal adaptive response. There is evidence that this is mediated by projections of the dorsal raphe nucleus and associated 5HT2 and 5HT3 receptors. Projections of the median raphe nucleus and associated 5HT1A receptors appear to mediate resilience to aversive events once they have occurred or if they persist. When this system breaks down depression results. It will be argued that all effective antidepressants act on 5HT1A, natural mechanisms of resilience.
 ...
PMID:Depression and 5HT. 180 32

Neuropeptide and neuroendocrine studies in the two major 'functional' psychotic illnesses have been reviewed. Changes in schizophrenia suggest both central dopamine dysfunction and hypothalamic, and perhaps, limbic pathology. In affective disorders, disruption of rhythmic neuroendocrine control seems to be evident, possibly mediated by either abnormal 5-hydroxytryptamine receptor function, non-specific hypothalamic derangement, or both. It is conceivable that some neuroendocrine changes in depression are trait phenomena which may be markers or mechanisms of vulnerability. The interaction of neuropeptide function and neuroendocrine state in psychotic illness is likely to be the focus of intensive future research.
 ...
PMID:Neuroendocrine dysfunction in psychotic disorders (excluding ACTH). 203 24

L-5-Hydroxytryptophan (5HTP) was administered to 20 patients suffering from panic disorder and to 20 healthy controls. Subjects received 60 mg 5HTP in 300 ml saline solution. Before, during, and up to 2 hours after 5HTP administration, symptoms of anxiety and depression were assessed. In addition, plasma 5HTP, 3-methoxy-4-hydroxyethylglycol (MHPG), cortisol, beta-endorphin, and melatonin levels were measured at several time points, and the kinetics of 5-hydroxytryptamine (5HT) in blood platelets were measured. During and after the infusion of 5HTP, none of the patients showed an increase in anxiety or depressive symptoms, despite the presence of severe side effects. Some patients even experienced the 5HTP infusion as a relief. In contrast to the patients, nine control subjects reported depressed mood, although no increases in anxiety were noted. In both patients and controls, the 5HTP infusion led to substantial increases in plasma cortisol and beta-endorphin levels, while the plasma MHPG level was unchanged. Plasma melatonin increased significantly after 5HTP administration, suggesting that increasing 5HT availability in man might affect melatonin synthesis. The results of this study are at odds with the hypothesis that there is a supersensitivity of 5HT2 receptors in panic disorder.
 ...
PMID:Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder. 213 31


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