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)

1. Ussing chambers were used to study the effects of the specific N-type Ca2+ channel antagonist, omega-conotoxin GVIA, on neurally evoked secretion across isolated submucosa/mucosa preparations from the small intestine of the guinea-pig. 2. Cholinergic and non-cholinergic neurones were stimulated with 10 microM dimethylphenylpiperazinium (DMPP). Non-cholinergic secretomotor neurones were preferentially stimulated with 100 nM 5-hydroxytryptamine (5-HT), while cholinergic secretomotor neurones were preferentially stimulated with 3 microM 5-HT in the presence of the 5-HT2 receptor antagonist ketanserin (30 nM). 3. omega-Conotoxin GVIA (1 nM-1 microM) depressed the secretion evoked by DMPP in a concentration-dependent manner, but a substantial residual response was observed. Hyoscine (100 nM) significantly depressed secretion evoked by DMPP, but did not prevent further depression of secretion by omega-conotoxin GVIA. 4. The toxin was substantially more effective when the non-cholinergic secretomotor neurones were preferentially activated with 100 nM 5-HT, with a decrease in the response of more than 75% of the control value in the presence of 1 microM omega-conotoxin GVIA. 5. omega-Conotoxin GVIA (1 microM) was relatively ineffective against secretion evoked by preferential activation of cholinergic secretomotor nuerones with 3 microM 5-HT in the presence of 30 nM ketanserin, inhibiting the response by less than 33%. However, this inhibition was significant. Both 100 nM hyoscine and 300 nM tetrodotoxin abolished this effect of omega-conotoxin GVIA. 6. It is concluded that N-type Ca2+ channels play a major role in transmitter release from non-cholinergic secretomotor neurones, but are not important for release from cholinergic secretomotor neurones in the guinea-pig small intestine.
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PMID:Differential effects of omega-conotoxin GVIA on cholinergic and non-cholinergic secretomotor neurones in the guinea-pig small intestine. 915 32

The 5-hydroxytryptamine (5-HT) receptor(s) that mediate(s) contraction of the rat ileum longitudinal muscle was studied. 5-HT and alpha-methyl-5-HT equipotently induced contractions, whereas 5-methoxytryptamine and 2-methyl-5-HT (partial agonist) were less potent; this rank order of potency suggests involvement of a 5-HT2 receptor. Neither tetrodotoxin nor atropine affected the contraction to 5-HT, suggesting a smooth muscle localization of these 5-HT2 receptors. The presence of either a selective 5-HT2B (SB 204741), 5-HT3 (granisetron) or 5-HT4 (SB 204070) antagonist, slightly affected the contractions to 5-HT. Thus, they were also included in the organ bath solution in all subsequent experiments in order to pharmacologically isolate the main contractile component. Using (if possible) 5-HT2A receptor-selective concentrations, ketanserin, ritanserin, metergoline, spiperone, mianserin, methiothepin, mesulergine, methysergide and cisapride all inhibited the contractions to 5-HT, causing a depression of the curve to 5-HT (i.e. surmountable antagonism was not observed with any of the above agents). Comparison of the affinities of these compounds for the various 5-HT2 receptor subtypes revealed that the receptor involved in the contractions to 5-HT most closely resembles the 5-HT2A receptor. However, cinanserin at a concentration expected to inhibit 5-HT2A receptor-mediated effects, failed to affect the contractions to 5-HT. It is thus concluded that on the longitudinal smooth muscle of the rat ileum, at least a part of the contraction to 5-HT is mediated by 5-HT receptors resembling the 5-HT2A receptor subtype.
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PMID:5-HT receptor types in the rat ileum longitudinal muscle: focus on 5-HT2 receptors mediating contraction. 943 Jul 91

We investigated whether the vasoactive neurotransmitter serotonin (5-HT) is involved in cortical spreading depression (CSD)-associated hyperemia in the rat. We focused on the 5-HT2 receptor, which is engaged in 5-HT induced small arteriolar relaxation in cats, as well as on the 5-HT1D/1B receptor, the binding site of the potent antimigraine drug sumatriptan. In male barbiturate anaesthetized Wistar rats (n=25) CSDs were elicited by brain topical application of 1 M KCl, and the DC-potential and regional cerebral blood flow (rCBF, by Laser Doppler flowmetry) were measured over the same hemisphere through dura and thinned bone, respectively. Intravenous application of 8 mg/kg of the 5-HT2A/2C receptor antagonist ritanserin (group I; n=8) significantly reduced the hyperperfusion amplitude during CSD by approximately 44% (p<0.05, from 342+/-124 to 194+/-97%, baseline before CSD=100%), and prolonged its duration by approx. 30%. Vehicle alone (group II; n=4) did not affect CSD hyperperfusion. The highly selective 5-HT1D/1B receptor agonist 311C90 was given in two doses: 100 micrograms/kg i.v. (n=5) had no effect on CSD hyperperfusion, while 800 micrograms/kg (n=5) increased hyperperfusion significantly (p<0.05, from 224+/-86 to 310+/-148%). We conclude that serotonin is, probably via 5-HT2 receptors, involved in the modulation of the regional cerebral blood flow increase during CSD. Novel highly selective receptor antagonists may help to discriminate the differential contribution of various 5-HT receptor subspecies.
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PMID:Cortical spreading depression-associated hyperemia in rats: involvement of serotonin. 950 21

We investigated the effect of electroconvulsive treatment (ECT) on platelet 14C-serotonin uptake, 3H-paroxetine binding and 5-HT2 receptors in 12 patients (10 women and 2 men) unresponsive to pharmacological treatment. The mean numbers of ECTs given was 6.1 +/- 1.5. Mean treatment days was 14.6 +/- 3.8. Mean percent reduction in MADRS scores was 80.7 +/- 19.7 (p < 0.002). The number of 5-HT2 receptors increased significantly and uniformly after ECT (p = 0.011). There was no correlation between the degree of increase in 5-HT2 receptor densities and the reduction in MADRS scores after ECT. There was no difference in mean Bmax for platelet 3H-paroxetine binding before and after ECT. Bmax increased in six patients and decreased in six patients. The study shows an increase in platelet 5-HT2-receptor densities in depression after repeated ECT. Recognizing the similarities between 5-HT2 receptors in platelets and cerebral cortex, it seems reasonable to assume that a similar upregulation of cortical 5-HT2 receptors occurs after ECT.
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PMID:Increased platelet 5-HT2 receptor binding after electroconvulsive therapy in depression. 966 Oct 89

We tested the hypothesis that spinal plasticity elicited by chronic bilateral cervical dorsal rhizotomy (C3-C5; CDR) has functional implications for respiratory motor control. Surgery was performed on rats (CDR or sham-operated) 26 d before phrenic motoneurons were retrogradely labeled with cholera toxin. Rats were killed 2 d later, and their spinal cords were harvested and processed to reveal the cholera toxin-labeled phrenic motoneurons and serotonin-immunoreactive terminals. The number of serotonin-immunoreactive terminals within 5 micrometer of labeled phrenic motoneuron soma and primary dendrites increased 2.1-fold after CDR versus sham-operation. Time-dependent phrenic motor responses to hypoxia were compared among CDR, sham-operated, and control rats. Anesthetized, paralyzed, vagotomized, and artificially ventilated rats were exposed to three, 5 min episodes of isocapnic hypoxia (FiO2 = 0.11), separated by 5 min hyperoxic intervals (FiO2 = 0.5). One hour after hypoxia, a long-lasting, serotonin-dependent enhancement of phrenic motor output (long-term facilitation) was observed in both sham and control rats. After CDR, long-term facilitation was 108 and 163% greater than control and sham responses, respectively. Pretreatment of CDR rats with a 5-HT2 receptor antagonist (ketanserin tartrate, 2 mg/kg, i.v.) before episodic hypoxia prevented long-term facilitation and revealed a modest (-28 +/- 13%; p < 0.05) long-lasting depression of phrenic motor output. The results indicate that CDR: (1) increases serotonergic innervation of the phrenic motor nucleus; and (2) augments serotonin-dependent long-term facilitation of phrenic motor output. These results further suggest a form of plasticity based on changes in the capacity for neuromodulation.
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PMID:Cervical dorsal rhizotomy enhances serotonergic innervation of phrenic motoneurons and serotonin-dependent long-term facilitation of respiratory motor output in rats. 976 86

For nearly three decades, evidence supporting a role for aberrant serotonergic function in the pathogenesis of depression has accumulated; however, only recently have methodologies and radiotracers suitable for in vivo clinical assessment of depression become available. To date, only a few neurochemical imaging studies have been performed in actively depressed subjects. A preliminary study using single photon emission computed tomography (SPECT) has demonstrated decreased levels of serotonin (5-HT) transporters in the midbrain regions of subjects with major depression. Analysis of the 5-HT2 receptor using positron emission tomography (PET) has suggested that this receptor may not be altered significantly in the depressed brain but may increase in response to antidepressant treatment. These findings are supported by studies in secondary "poststroke" depression that have shown that elevations in 5-HT2 receptor density correlated with the alleviation of symptoms of depressed mood. With the rapid development of novel PET and SPECT radiotracers, future studies of the serotonergic system that evaluate presynaptic (5-HT transporter) and postsynaptic (5-HT1A and 5-HT2A receptors) markers and the interaction of synaptic levels of 5-HT with these sites will make profound contributions to the understanding of the role of the serotonergic synapse in the pathophysiology of depression.
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PMID:Imaging of the serotonergic system: interactions of neuroanatomical and functional abnormalities of depression. 978 77

Repetitive transcranial magnetic stimulation (rTMS) has been shown to affect mood in health and disease. Evidence to date has demonstrated an antidepressant potential for low- and high-frequency rTMS treatment. In animal behavioral models of depression magnetic stimulation of the brain induced similar effects to those of electroconvulsive shock (ECS). In this study the effects of repeated rTMS on rat brain noradrenaline, dopamine, serotonin and their metabolites levels, as well as on beta-adrenergic and 5-HT2 receptor characteristics were studied. After 10 days of treatment, beta-adrenergic receptors were significantly up regulated in the frontal cortex, down regulated in the striatum and were unchanged in the hippocampus. 5-HT2 receptors were down regulated in the frontal cortex and were not changed in the other brain areas. No change in benzodiazepine receptors in the frontal cortex and cerebellum were demonstrated. These findings demonstrate specific and selective alterations induced by repeated rTMS, which are distinct from those induced by other antidepressant treatments. TMS therapeutic effects in humans and behavioral and biochemical effects in animal, suggest that TMS has a unique mechanism of action which requires further investigation.
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PMID:Chronic repetitive transcranial magnetic stimulation alters beta-adrenergic and 5-HT2 receptor characteristics in rat brain. 987 93

Our previous findings indicated that electrical or chemical activation of the thalamic nucleus submedius (Sm) produced significant antinociceptive effects and that these effect were blocked by lesion or depression of the ventrolateral orbital cortex (VLO) or the periaqueductal gray (PAG) suggesting a role of the Sm in modulation of nociception. To further investigate the neurotransmitter mechanism involved in this nociceptive modulatory pathway, we tested the effects of microinjection of 5-hydroxytryptamine (5-HT, 50 mM, 0.5 microl) into Sm on the tail flick (TF) reflex. The results show that a unilateral microinjection of 5-HT into Sm significantly depresses the TF reflex; and that this effect is repeatable and dose-dependent. Furthermore, microinjection of 5-HT2 receptor antagonist cyproheptadine (CPT, 0.3 mM, 0.5 microl) into the same Sm site reverses this 5-HT-evoked inhibition of TF reflex. These results suggest that 5-HT application to the Sm may activate Sm neurons through the 5-HT2 receptors leading to activation of the brainstem descending inhibitory system via the VLO and depression of the nociceptive information at the spinal level.
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PMID:Inhibitory effects of 5-hydroxytryptamine microinjection into thalamic nucleus submedius on rat tail flick reflex are mediated by 5-HT2 receptors. 1002 5

The lateral superior olive (LSO) is a primary site of binaural convergence that responds selectively to changes in interaural level difference (ILD) by integrating ipsilateral excitatory and contralateral inhibitory inputs. The circuit matures during the first three postnatal weeks, undergoing several structural and functional changes that are influenced by afferent activity. Therefore modulation of synaptic activity by neuromodulators may participate in the maturation of this circuit. The present study describes robust effects of serotonin (5-HT) on LSO synaptic function. Using whole cell voltage-clamp recording from gerbil LSO neurons (postnatal days 6-13) in an in vitro slice preparation, we have identified several distinct forms of serotonergic modulation of spontaneous and evoked synaptic transmission. First, 1-2 min application of 5-HT (100 microM) activated prolonged bursts of spontaneous inhibitory postsynaptic currents (IPSCs). However, there was an age-dependent decline, such that this effect rarely was observed beyond postnatal day 8. 5-HT apparently increased the excitability of inhibitory afferents, because 5-HT-induced IPSCs were blocked by tetrodotoxin. A second effect of 5-HT was to depress rapidly and profoundly the amplitude of electrically evoked excitatory postsynaptic currents (EPSCs). In contrast, 5-HT also depressed evoked IPSCs but to a significantly lesser degree. The receptor subtypes mediating these effects were examined using specific 5-HT agonists and antagonists. A 5-HT1 agonist, 5-carboxamidotryptamine, produced EPSC depression but did not induce spontaneous IPSCs. A 5-HT2 agonist, alpha-Me-5-HT, reproduced all the observed effects of 5-HT (PSC depression as well as induction of spontaneous IPSCs), whereas a 5-HT2 antagonist, ketanserin, blocked the induction of spontaneous IPSCs. Therefore induction of spontaneous IPSCs is mediated by 5-HT2 receptors, whereas both 5-HT1 and 5-HT2 receptor types contribute to PSC depression. Serotonergic modulation of LSO synapses may have consequences for both developmental plasticity and auditory function. Serotonergic induction of IPSCs was observed primarily in young animals and thus may represent a mechanism for amplifying the activity of inhibitory synapses in LSO during a period of use-dependent plasticity in postnatal development. PSC depression, which preferentially affects excitation, is a potential mechanism for modulation of ILD tuning.
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PMID:Serotonergic modulation of synapses in the developing gerbil lateral superior olive. 1036 94

Selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy in depression and anxiety disorders. This raises the question of how the single action of serotonin reuptake inhibition can improve several psychiatric conditions. In order to understand this apparent paradox it is necessary to consider where SSRIs act in the pathogenic process underlying depression or anxiety disorders. Tryptophan depletion has been used extensively in research into depression and has shown that, in patients receiving an SSRI whose depression is in remission, depleting serotonin leads to recurrence of the disorder. Similar results have been found for panic disorder. This suggests that increased levels of serotonin are necessary in the synapse for the SSRI to be effective in the treatment of depression and panic disorder. In obsessive compulsive disorder, depletion of serotonin in patients recovered on an SSRI does not cause relapse; receptor adaptation may be more important. Variations within the SSRI drug class, such as the selectivity ratios for serotonin versus noradrenaline uptake, elimination half-life, and affinity for the 5-HT2 receptor have been identified and may be important determinants of efficacy, side effects and clinical use.
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PMID:Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders. 1052 62


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