UMLS:C0011570 - FACTA Search

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

Previous in vitro studies demonstrated that long-term potentiation (LTP) could be elicited at medial perforant path (MPP) synapses onto hippocampal granule cells in slices from 7-day-old rats. In contrast, in vivo studies suggested that LTP at perforant path synapses could not be induced until at least days 9 or 10 and then in only a small percentage of animals. Because several characteristics of the oldest granule cells are adult-like on day 7, we re-examined the possibility of eliciting LTP in 7-day-old rats in vivo. We also recorded from 8- and 9-day-old rats to further elucidate the occurrence and magnitude of LTP in neonates. With halothane anesthesia, all animals in each age group exhibited synaptic plasticity of the excitatory postsynaptic potential following high-frequency stimulation of the MPP. In 7-day-old rats, LTP was elicited in 40% of the animals and had an average magnitude of 143%. Long-term depression (LTD) alone (magnitude of 84%) was induced in 40% of the animals, while short-term potentiation (STP) alone (magnitude of 123%) was induced in 10%. STP followed by LTD was elicited in the remaining 10%. Data were similar for all ages combined. In addition, the N-methyl-d-aspartate (NMDA) antagonist (R,S)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) blocked the occurrence of LTP at each age and doubled the percentage of animals expressing LTD alone for all ages combined. These results demonstrate that tetanic stimulation can elicit LTP or LTD at MPP synapses in 7-day-old rats, supporting our premise that at least a portion of the dentate gyrus is functional at this early age.
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PMID:In vivo recordings of long-term potentiation and long-term depression in the dentate gyrus of the neonatal rat. 1464 75

The purpose of the study was to test the hypothesis that borderline personality disorder (BPD) and its underlying traits are associated with abnormalities in neurotransmitter systems. Subjects were 30 women with BPD and 22 normal controls, assessed using the Diagnostic Interview for Borderlines, revised, the Hamilton Depression Scale (HAM-A) and the Hamilton Anxiety Scale (HAM-A), the Diagnostic Assessment of Personality Pathology, the Buss-Durkee Guilt-Hostility Inventory, the Barratt Impulsivity Scale (BIS), and challenge tests to measure serotonergic, cholinergic and noradrenergic activity. Borderline subjects with high HAM-A and HAM-D scores showed a faster time to peak in prolactin response to meta-chlorphenylpiperazine (m-CPP) challenge. Borderline subjects with high BIS scores showed prolactin blunting. There were no differences in cortisol response to m-CPP, or on the cholinergic and noradrenergic challenges. The results suggest that impulsive traits in borderline patients are associated with abnormalities in serotonergic systems.
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PMID:Neurobiological correlates of diagnosis and underlying traits in patients with borderline personality disorder compared with normal controls. 1467 43

The subiculum is a limbic cortical region that receives inputs from hippocampus and other parahippocampal regions. We used horizontal brain slices to study the modulatory effects of muscarinic receptor activation on excitatory afferent systems of the subiculum. Multiple inputs are preserved in these slices. Carbachol (CCh, applied to the bath) induced a decrease in the field responses (40-50% at 50 microM; 60% at 100 microM) to CA1, presubicular (PreS), and medial entorhinal (MEC) stimulation. Subicular responses to lateral entorhinal (LEC) stimuli were not depressed. The M1 receptor antagonist pirenzepine at 1 microM was sufficient to reverse most of the CCh-induced depression of afferent excitation, but 10 microM concentrations were required to eliminate the CCh-induced firing in the isolated subiculum. A partial reversal of the CCh-induced depression of afferent excitation was achieved by the M2 receptor antagonist methoctramine (1 or 10 microM), but these concentrations did not prevent CCh-induced firing. When CA1 afferents were repetitively activated with submaximal stimuli in the presence of CCh, population excitatory postsynaptic potentials (EPSPs) showed modest summation, but every response was smaller than a corresponding events in normal media. Population spikes, particularly late spikes in a train, showed pronounced facilitation during CCh exposure. The NMDA receptor antagonist CPP (10 microM) prevented facilitation of responses to repetitive stimulation in the presence of carbachol. We conclude that CA1, PreS, and MEC afferents to the subiculum exhibit CCh sensitivity similar to that established for area CA3 afferents to CA1, and LEC afferents to subiculum exhibit CCh resistance. Our data suggest that much of the hippocampal formation circuitry is modulated by CCh and the properties of this modulation can explain some specific firing characteristics of hippocampal formation neurons in "cholinergic" versus "noncholinergic" brain states.
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PMID:Differential modulation by carbachol of four separate excitatory afferent systems to the rat subiculum in vitro. 1539 Jan 73

High-frequency stimulation of lateral perforant path is accompanied by a heterosynaptic long-term depression (LTD) of medial perforant path synaptic responses in both the dentate gyrus and the CA3 region of the hippocampus. We reported previously that LTP induction at lateral perforant path-CA3 synapses is unaffected by NMDA antagonists. However, it is not known if heterosynaptic LTD that is observed in the CA3 region following lateral perforant path stimulation also is independent from NMDA receptors. We address this question in anesthetized adult rats using systemic administration of the competitive NMDA receptor antagonist CPP. Induction of lateral perforant path-CA3 LTP produced a sustained heterosynaptic depression of medial perforant path-CA3 responses. Systemic administration of CPP (10 mg/kg) was ineffective in blocking the induction of LTP at lateral perforant path-CA3 responses. However, heterosynaptic LTD of medial perforant path-CA3 responses was blocked completely by CPP. These data indicate that NMDA receptors are not required for the induction of lateral perforant path-CA3 LTP, but are involved in the induction of heterosynaptic LTD that accompanies lateral perforant path activity. The requirement for NMDA receptors for heterosynaptic LTD suggests one functional role of NMDA receptors at termination fields of the lateral perforant path.
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PMID:NMDA receptor antagonists block heterosynaptic long-term depression (LTD) but not long-term potentiation (LTP) in the CA3 region following lateral perforant path stimulation. 1563 91

Trazodone is an effective antidepressant drug with a broad therapeutic spectrum, including anxiolytic efficacy. Although trazodone is usually referred to as a serotonin (5-HT) reuptake inhibitor, this pharmacological effect appears to be too weak to fully account for its clinical effectiveness. The present study aimed to elucidate the agonist properties of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP), at 5-HT(1A) receptors by means of the guanosine-5'-O-(3-[(35)S]thio)-triphosphate ([(35)S]GTPgammaS) binding assay. In membranes prepared from Chinese hamster ovary cells expressing human 5-HT(1A) receptors (CHO/h5-HT(1A)), trazodone behaved as an almost full agonist and m-CPP was also a highly efficacious partial agonist at 5-HT(1A) receptors. The intrinsic activities of both compounds were higher than those of tandospirone and buspirone, which are clinically effective anxiolytics with well-known 5-HT(1A) partial agonist properties. These effects were replicated in the 5-HT(1A) receptor-mediated [(35)S]GTPgamma(S) binding assay in native rat brain membranes (at least in hippocampal membranes), although the intrinsic activities of the compounds were low and differently ranked compared to those in CHO/h5-HT(1A) cell membranes. When considering the implications of 5-HT(1A) receptors in anxiety and/or depression, as well as the clinical effectiveness of azapirone anxiolytics with partial 5-HT(1A) receptor agonist properties such as buspirone, it is possible that the agonist effects on 5-HT(1A) receptors of trazodone and its active metabolite m-CPP presented in this study contribute, at least in part, to the clinical efficacy of the atypical antidepressant trazodone.
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PMID:Trazodone and its active metabolite m-chlorophenylpiperazine as partial agonists at 5-HT1A receptors assessed by [35S]GTPgammaS binding. 1588 8

Trazodone is an antidepressant agent used in Spain since 1975. There are few documented reports of fatalities solely attributed to trazodone and none in which the main metabolite is analyzed. A fatal case of self-poisoning following oral ingestion is reported along with a description of the validated analytical methods involved, a discussion of poisoning characteristics, and a review of reports describing trazodone overdose cases with analytical results. The deceased was an 86-year-old man with cancer, who suffered depression. He went to see his doctor in a primary health care unit and told him he had just taken an unknown amount of tablets of Deprax to commit suicide. The doctor induced emesis as a first emergency measure. His death occurred before arriving to the hospital, and he left a suicide note nearby. Systematic toxicological analysis of postmortem blood used routinely in our laboratory revealed the presence of trazodone 4.9 mg/L and m-chlorophenyl-piperazine (m-CPP) 0.6 mg/L, its active and major metabolite. In addition, metamizol 19.6 mg/L and 4-methyl-amino-antipyrine (4-MAA) 40.7 mg/L, its active metabolite, were also found in blood. All drugs and metabolites involved in the case were detected using gas chromatography-nitrogen-phosphorus detection (GC-NPD) and confirmed using gas chromatography-mass spectrometry (GC-MS) mode total ion chromatogram. An additional high-performance liquid chromatography-diode array detection (HPLC-DAD) screening also obtained the same results. Quantitation of trazodone together with its metabolite in blood was carried out using GC-NPD, while quantitation of metamizol was performed using HPLC-DAD. Limits of detection for trazodone and m-CPP were 33 and 11 microg/L, respectively, absolute recoveries were more than 86% and 75%, respectively, intra-assay precisions less than 4%, interassay precisions less than 5%, and linearity up to 2.0 mg/L. Limit of detection for metamizol was 1117 microg/L, absolute recovery more than 84%, intra-assay precision less than 8%, interassay precision less than 12%, and linearity up to 48 mg/L. Based on the autopsy findings, patient history, toxicology results, and previously reported trazodone intoxications, the forensic pathologists ruled that the cause of death was due to an overdose of trazodone, and the manner of death was listed as suicide.
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PMID:Investigation of a fatality due to trazodone poisoning: case report and literature review. 1597 58

The present study investigated the role of NMDA receptors in behavioral and neuroplastic changes in amygdala efferent (central amygdala to periaqueductal gray-ACE-PAG) and amygdala afferent (ventral angular bundle to basolateral amygdala-VAB-BLA) pathways in response to predator stress. Effects on brain and behavioral response to predator stress of competitive block of NMDA receptors with a dose of 10 mg/kg of CPP (3-(2-carboxypiperazin4-yl)propyl-l-phosphonic acid) were studied. Behavioral response to stress was tested with hole board, elevated plus maze, light/dark box, social interaction and acoustic startle tests. CPP was administered i.p. 30 min prior to predator stress and blocked the effects of predator on some but not all behaviors measured 8-9 days later. Effects of predator stress and CPP on potentials evoked in the PAG by single pulse stimulation of the ACE and in the BLA by single pulse stimulation of VAB were assessed 10-11 days after predator stress. Predator stress potentiated ACE-PAG evoked potentials in the right but not the left hemisphere, replicating previous work. Predator stress potentiated VAB-BLA transmission in both hemispheres 10-11 days after predator stress. Right hemisphere VAB-BLA potentiation replicated and extended past studies showing right hemisphere potentiation at 1 and 9 days after stress. Left VAB-BLA potentiation effects differed from the long term depression seen in VAB-BLA at 1 and 9 days after stress in previous studies. CPP blocked predator stress-induced potentiation of ACE-PAG and VAB-BLA evoked potentials in the right hemisphere. CPP did not block left VAB-BLA potentiation, rather CPP amplified it. Left hemisphere effects of CPP were interpreted as reflecting block of NMDA dependent long term depression, which unmasked a non-NMDA dependent potentiation. Taken together, the findings add to a body of evidence suggesting that a syndrome of behavioral changes follows predator stress. Components of this syndrome likely depend on changes in separable neural substrates. Potentiation of ACE-PAG and VAB-BLA evoked potentials in the right hemisphere likely mediates a subset of changes in behavior. Moreover, a medial ACE-PAG pathway is implicated in mediating stress-induced changes in startle amplitude. In contrast, a lateral ACE-PAG pathway is implicated in mediating changes in startle habituation. Finally, consistent with cat and human studies, the right hemisphere appears particularly important in long term response to stress.
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PMID:Role of NMDA receptors in the lateralized potentiation of amygdala afferent and efferent neural transmission produced by predator stress. 1610 87

Long-term morphological synaptic changes associated with homosynaptic long-term potentiation (LTP) and heterosynaptic long-term depression (LTD) in vivo, in awake adult rats were analyzed using three-dimensional (3-D) reconstructions of electron microscope images of ultrathin serial sections from the molecular layer of the dentate gyrus. For the first time in morphological studies, the specificity of the effects of LTP and LTD on both spine and synapse ultrastructure was determined using an N-methyl-d-aspartate (NMDA) receptor antagonist CPP (3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid). There were no differences in synaptic density 24 h after LTP or LTD induction, and CPP alone had no effect on synaptic density. LTP increased significantly the proportion of mushroom spines, whereas LTD increased the proportion of thin spines, and both LTP and LTD decreased stubby spine number. Both LTP and LTD increased significantly spine head evaginations (spinules) into synaptic boutons and CPP blocked these changes. Synaptic boutons were smaller after LTD, indicating a pre-synaptic effect. Interestingly, CPP alone decreased bouton and mushroom spine volumes, as well as post-synaptic density (PSD) volume of mushroom spines.These data show similarities, but also some clear differences, between the effects of LTP and LTD on spine and synaptic morphology. Although CPP blocks both LTP and LTD, and impairs most morphological changes in spines and synapses, CPP alone was shown to exert effects on aspects of spine and synaptic structure.
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PMID:The N-methyl-D-aspartate receptor antagonist CPP alters synapse and spine structure and impairs long-term potentiation and long-term depression induced morphological plasticity in dentate gyrus of the awake rat. 1996 8

The cognition-enhancing properties of deramciclane (N,N-dimethyl-2-([(1R,4R,6S)-1,7,7-trimethyl-6-phenyl-6-bicyclo[2.2.1]heptanyl]oxy)ethanamine) and memantine (3,5-dimethyl-tricyclo[3.3.1.1(3,7)]decylamine-3,5-dimethyladamantan-1-amine) were evaluated in the novel object recognition (OR) test in the rat, while their effect in comparison with other N-methyl-D-aspartate (NMDA) receptor blockers such us MK-801 ([+]-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate) and CPP ([+/-]-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) on NMDA-evoked spreading depression (SD) was investigated in the chicken retina, in vitro. In the OR test, pretreatment of rats with either deramciclane (30 mg/kg p.o.) or memantine (10 and 30 mg/kg, p.o.) resulted in preference for the novel object, compared to the familiar one, indicating procognitive activity of the compounds. In the in vitro studies memantine (10-30 M), or deramciclane (30-100 M) as well as CPP (0.1-1 M), MK-801 (0.3-1 M), concentration-dependently inhibited NMDA evoked SD. Furthermore, the inhibitory effect of memantine, deramciclane and MK-801 was activity-dependent. These results support the role of NMDA receptors in the procognitive effect of deramciclane.
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PMID:Deramciclane improves object recognition in rats: potential role of NMDA receptors. 1996 3

Alterations in curvature of the post synaptic density (PSD) and apposition zone (AZ), are believed to play an important role in determining synaptic efficacy. In the present study we have examined curvature of PSDs and AZs 24 h following homosynaptic long-term potentiation (LTP), and heterosynaptic long-term depression (LTD) in vivo, in awake adult rats. High frequency stimulation (HFS) applied to the medial perforant path to the dentate gyrus induced LTP while HFS stimulation of the lateral perforant path induced LTD in the middle molecular layer of the dentate gyrus (DG). Curvature changes were analysed in this area using three dimensional (3-D) reconstructions of electron microscope images of ultrathin serial sections. Very large and significant changes in 3-D measurements of AZ and PSD curvature occurred 24 h following both LTP and LTD, with a flattening of the normal concavity of mushroom spine heads and a change to convexity for thin spines. An N-methyl-D-aspartate (NMDA) receptor antagonist CPP (3-[(R)-2-Carboxypiperazin-4-yl]-propyl-1-phosphonic acid) blocked the changes in curvature of mushroom and thin spine PSDs and apposition zones, actually increasing the concavity of mushroom spines as the spine engulfed the presynaptic bouton. In order to establish whether these changes resulted from the effect of the NMDA antagonist or from its coincidence with synaptic activation during testing we examined the effects of CPP alone on PSD and apposition zone curvature. It was found that CPP alone also caused a small decrease in curvature of both PSD and apposition zone of mushroom and thin spines.
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PMID:Alterations in synaptic curvature in the dentate gyrus following induction of long-term potentiation, long-term depression, and treatment with the N-methyl-D-aspartate receptor antagonist CPP. 2084 31

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