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)

The evidence accumulated so far indicates that seizure activity exerts profound changes on the metabolism of opioid peptides in the hippocampus. Our data consistently show a large transient decrease in dynorphin and a modest decrease in enkephalin in the hippocampus following either a single ECS or KA injection. These initial reductions, which are indicative of increased release, may trigger the biosynthetic process of hippocampal opioids and result in an overproduction of the peptides seen in the rebound phase. However, the amount and timing of the rebound in enkephalin and dynorphin levels in response to repeated ECS, amygdaloid kindling, or KA differ drastically: a rapid and sustained increase in ME-LI follows all three treatments, in contrast to a slow recovery after a large and sustained decrease in DN-LI induced by repeated ECS and amygdaloid kindling. These results, which are unique to the hippocampus, suggest that differential mechanisms are operative in regulating the metabolism of these two opioid peptides in the hippocampus. It is likely that a well-coordinated regulation of hippocampal function can be achieved through the differential release of enkephalin and dynorphin and their subsequent interactions at different subtypes of opioid receptors following seizure activities. From a functional point of view, our data provide a neurochemical correlate of previous reports that brain opioid peptides may mediate ECS-induced behavioral alterations, such as changes in seizure threshold, postictal depression, and retrograde amnesia. The robust changes in the levels of opioid peptides in kindled rats, plus shortening of the kindling process by pretreatment with mu opioid antagonists, strongly suggest the involvement of brain opioid peptides in the development of kindling. Finally, these studies show clear evidence that enkephalin in the hippocampus is important in KA-induced WDS, a component of the opiate withdrawal syndrome in rodents (Isaacson and Lanthorn 1981). Further studies should help distinguish the regulatory mechanisms responsible for changes in opioid peptide metabolism during states of hyperexcitability in the hippocampal formation.
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PMID:Seizure-induced alterations in the metabolism of hippocampal opioid peptides suggest opioid modulation of seizure-related behaviors. 289 42

Those antidepressant drugs that are in wide clinical use decrease response rate and increase reinforcement rate when administered to rats performing on a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule. Drugs that are not antidepressants do not have this effect. In this experiment, the following were examined for their effects on a DRL 72-s schedule: trazodone, zimelidine, fluoxetine, and bupropion (atypical antidepressants); electroconvulsive shock (ECS, which is an effective treatment for depression); and haloperidol and clozapine (antipsychotic drugs). Trazodone (3.12-25.00 mg/kg), fluoxetine (10-20 mg/kg), and ECS decreased response rate and increased reinforcement rate. Zimelidine (20 mg/kg) increased reinforcement rate and nonsignificantly decreased response rate. At doses between 2.5 and 40 mg/kg, bupropion had no effect on reinforcement rate or response rate, but at 60 mg/kg response rate was increased and reinforcement rate was nonsignificantly decreased. At the higher dose, the effects of bupropion resemble those of a psychomotor stimulant. Haloperidol (0.04 mg/kg) and clozapine (2.5-10.0 mg/kg) decreased response rate and reinforcement rate. These results suggest that the DRL 72-s schedule may be useful for testing the antidepressant potential of new drugs.
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PMID:Behavioral screen for antidepressants: the effects of drugs and electroconvulsive shock on performance under a differential-reinforcement-of-low-rate schedule. 316 Nov 16

The esophageal atrial cardiac stimulation was applied to 93 patients divided into 4 groups: patients with typical, probable and atypical angina pectoris and clinically healthy controls. The tests positive for ischemic heart disease are classified into 3 classes according to the duration of ECG ischemic changes: I class--the ischemic changes are registered during the time of the test only; II class--the changes are seen in the first ECS complexes after the stimulation and III class--the changes persist after the second minute following the esophageal atrial stimulation. The test was worked out to diagnostic criteria in 92.5% of the cases and is undoubtedly positive in 77.5% of the patients with typical and probable stenocardia and in 36.6% of the patients with atypical precordial pain. Most important for the diagnosis of ischemic heart disease are: the early occurrence of ST-depression before the submaximal pulse rate is reached, registration of II and III degree of ST-depression and the appearance of chest pain during the time of the test. The esophageal atrial stimulation is a valuable method for the diagnosis of ischemic heart disease and it is surprisingly easy to perform. The method is harmless and can be applied to patients to whom the physical exercise test cannot be applied.
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PMID:[Esophageal precordial cardiac stimulation in the diagnosis of ischemic heart disease]. 324 14

From the evidence reviewed above, there is little doubt that ECS activates endogenous opioids and modifies their receptors. Thus, this form of SIA is accompanied by many other corollaries of opioid-like actions, including catalepsy, similar EEG patterns, common autonomic effects, and increases in opioid receptor binding sites. Investigations have further indicated that the amnestic effects of ECS can also be attenuated by naloxone, and that pituitary-derived opioids may play an important role as a predominant source of opioids that contribute to these opioid-like effects following ECS. It is hoped that these many attempts to correlate SIA with other behavioral and physiological endpoints following ECS will provide a more global perspective on the role of endogenous opioid systems in ECS. From these results, it is suggested that other forms of SIA may also share many of these properties in common with ECS-induced SIA. Nonetheless, ECS and other forms of SIA, such as cold water exposure and restraint, share with ECS a common history of clinical use in the treatment of human depression. It is possible that the common thread linking these experimental observations to endogenous opioid systems may provide new insights into the cause and treatment of mental disorders as well as the perception of pain.
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PMID:Electroconvulsive shock activates endogenous opioid systems: behavioral and biochemical correlates. 352 81

The effects of natural and synthetic sauvagine on locomotor activity and ECS-induced seizures were studied in DBA/2 mice. A dose-dependent activity depression was evident following the administration of both compounds. Moreover they exerted a protective effect against ECS-induced seizures. This effect was naloxone-reversible, suggesting the involvement of endogenous opioids. In both series of experiments natural sauvagine was more effective than the synthetic compound.
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PMID:Effects of sauvagine on behavioural arousal of mice. 383 73

Forty-nine patients with coronary atherosclerosis (according to the results of selective angiography), whose ages ranged from 29 to 59 years, were examined. Comparison with the results of ECG at rest and the findings of coronarography showed no changes in the QRS complex in 16% of patients with lesions of two and in 10% of those with obstructive changes in three main coronary artery. Displacement of the ST segment as a sign of myocardial ischemia during physical exercise tests in leads V5--V6 of the ECG coincided with obstructive lesions of the left coronary artery in 91% of cases. Patients suffering from obstructive lesions of the right coronary artery with or without atherosclerotic changes in the left coronary artery reacted by depression of the ST segment in the II, III, and aVF leads of the ECS. The authors suggest that there exists a mechanism of "intracoronary steal" of perfusion blood supply when the ischemic changes on the ECG do not coincide with the localization of coronary atherosclerosis.
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PMID:[Electrocardiographic criteria of probable localization of coronary arteriosclerosis]. 720 48

Rats were studied (a) after a single transauricular electroshock (acute ECS) and (b) following 10 consecutive once-daily shocks (chronic ECS). ECS produced a generalized convulsion marked by a polyspike EEG seizure. The seizure was followed by a period of postictal depression (PID) characterized by EEG high-voltage synchrony, EMG quietening, and an associated stuporous behavior in the rat. Acute ECS produced a maximal of 33 +/- 8 (S.E.) percent above control in the EEG voltage output during postictus, with the PID lasting 2680 +/- 658 sec. Chronic ECS resulted in a significant enhancement of these acute responses. Pretreating rats with naloxone (0.3-10 mg/kg s.c.) antagonized the postictal effects of acute ECS, but not of chronic ECS. These naloxone-sensitive postictal EEG and behavioral changes appear to reflect a release of endogenous opioid peptides during ictus, a finding consistent with the hypothesis that electroshock activates opioid systems.
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PMID:Opiate-like electroencephalographic and behavioral effects of electroconvulsive shock in rats. 733 52

The effects of electroconvulsive seizure and anti-convulsant drugs on induction of mRNA of heat shock protein were studied in mouse brain. Electrical shock induced mRNA of heat shock cognate protein (HSC70), but not heat shock protein (HSP70) mRNA. The induction was maximum 1 h after the ECS and continued for several hours, followed by long-lasting depression. Diazepam slightly prevented the ECS, but strongly attenuated the induction of HSC70 mRNA. Whereas phenytoin, which blocked the seizure, did not decrease but delayed the induction of HSC70 mRNA. The present results suggest that HSC70 mRNA level is increased with the ECS and that the induction level did not necessarily correlate the severity of the seizure.
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PMID:Correlation between electroconvulsive seizure and HSC70 mRNA induction in mice brain. 823 52

The physicochemical properties of water enable it to act as a solvent for electrolytes, and to influence the molecular configuration and hence the function--enzymatic in particular--of polypeptide chains in biological systems. The association of water with electrolytes determines the osmotic regulation of cell volume and allows the establishment of the transmembrane ion concentration gradients that underlie nerve excitation and impulse conduction. Fluid in the central nervous system is distributed in the intracellular and extracellular spaces (ICS, ECS) of the brain parenchyma, the cerebrospinal fluid, and the vascular compartment--the brain capillaries and small arteries and veins. Regulated exchange of fluid between these various compartments occurs at the blood-brain barrier (BBB), and at the ventricular ependyma and choroid plexus, and, on the brain surface, at the pia mater. The normal BBB is relatively permeable to water, but considerably less so to ions, including the principal electrolytes Brain fluid regulation takes place within the context of systemic fluid volume control, which depends on the mutual interaction of osmo-, volume-, and pressure-receptors in the hypothalamus, heart and kidney, hormones such as vasopressin, renin-angiotensin, aldosterone, atriopeptins, and digitalis-like immunoreactive substance, and their respective sites of action. Evidence for specific transport capabilities of the cerebral capillary endothelium, for example high Na+K(+)-ATPase activity and the presence at the abluminal surface of a Na(+)--H+ antiporter, suggests that cerebral microvessels play a more active part in brain volume regulation and ion homoeostasis than do capillaries in other vascular beds. The normal brain ECS amounts to 12-19% of brain volume, and is markedly reduced in anoxia, ischaemia, metabolic poisoning, spreading depression, and conventional procedures for histological fixation. The asymmetrical distributions of Na+ K+ and Ca2+ between ICS and ECS underlie the roles of these cations in nerve excitation and conduction, and in signal transduction. The relatively large volume of the CSF, and extensive diffusional exchange of many substances between brain ECS and CSF, augment the ion-homeostasing capacity of the ECS. The choroid plexus, in addition to secreting CSF principally by biochemical mechanisms (there is an additional small component from the extracellular fluid), actively transports some substances from the blood (e.g. nucleotides and ascorbic acid), and actively removes others from the CSF. In contrast with CSF secretion, CSF reabsorption is principally a biomechanical process, passively dependent on the CSF-dural sinus pressure gradient. Pathological increases in intracranial water content imply development of an intracranial mass lesion. The additional water may be distributed diffusely within the brain parenchyma as brain oedema, as a cyst, or as increase in ventricular volume due to hydrocephalus. Brain oedema is classified on the basis of pathophysiology into four categories, vasogenic, cytotoxic, osmotic and hydrostatic. The clinical conditions in which brain oedema presents the greatest problems are tumour, ischaemia, and head injury. Peritumoural oedema is predominantly vasogenic and related to BBB dysfunction. Ischaemic oedema is initially cytotoxic, with a shift of Na+ and CI- ions from ECS to ICS, followed by osmotically obliged water, this shift can be detected by diffusion-weighted MRI. Later in the evolution of an ischaemic lesion the oedema becomes vasogenic, with disruption of the BBB. Recent imaging studies in patients with head injury suggest that the development of traumatic brain oedema may follow a biphasic time course similar to that of ischaemic oedema. Hydrocephalus is associated in the great majority of cases with an obstruction to the circulation or drainage of CSF, or, occasionally, with overproduction of CSF by a choroid plexus papilloma. In either case, the consequence is a ris
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PMID:The normal and pathological physiology of brain water. 907 71

Sismotherapy (ST) brings about numerous neurobiological changes, particularly changes in neuromediators and their receptors, second messengers, neuropeptides and neurotropic factors, a number of which are hypothesized to play a role in the pathophysiology or therapeutics of affective disorders (M. Fink). What is not yet known is which of these mechanisms is crucial for the psychotropic and anticonvulsant effects of ST. However, it is clear that the effects of ST tend to be relatively acute, and do not attack the deep-seated abnormalities that are the underlying causes of recurrences of affective disorders. This is corroborated by the fact that in animals, most of the effects of ECS on catecholamines and their receptors (and on receptors for benzodiazepines or neuropeptides such as TRH) tend to be relatively transient, and in most cases have been found to represent compensatory adaptations to the induced motor convulsions. However, recent preclinical data using attenuation, and clinical findings using reiterated transcranial magnetic stimulation (rTMS), suggest that it may not be necessary to provoke a clonic convulsion in order to achieve the beneficial psychotropic and anticonvulsant effects of ST. In rodents receiving stimulation to the cerebellar tonsil, seven daily subacute low-frequency sessions (stimulation at 1 Hz for 15 minutes) produced clear improvement in clonic convulsions and in post-discharge thresholds, together with durable inhibition of convulsions when stimulation was resumed (Weiss et al., 1995). Stimulation at 1 Hz for 15 minutes was more effective than stimulation at 10 or 20 Hz in attenuating convulsions. Although reiterated ECS also induced an anti-triggering effect, this dissipated rapidly over five days (Post et al., 1984). It is of great interest that recent publications have shown that rTMS at 10 or 20 Hz to the left frontal cortex, administered to patients suffering from refractory depression (George et al., 1995) or to patients (hospitalised or not) with milder degrees of depression (Pasquale-Leon et al., 1996), had a moderate or marked antidepressant effect. In these studies, rTMS showed few unwanted effects (other than mild pain in some patients, due to contraction of the temporal muscles); it did not induce motor convulsions, and did not, as such, appear to be associated with the memory loss described in subjective accounts or in preliminary neuropsychological tests (Little and Kimbrell et al., 1996). The optimal frequencies, durations and positions for rTMS to maximise its antidepressant effect still remain to be determined. However, the first controlled and open studies have tended to show that (because of the capacity of rapid magnetic fluxes to produce sub-convulsant electrical discharges that are relatively localised in the brain), rTMS may be found to be a clinically useful antidepressant model. This would suggest the possibility that some of the neurochemical changes induced by the clonic convulsions of ECS could be directly induced by stimulation at the very edge of the threshold (but still below it); this would open up the hope that one day these endogenous neurochemical processes could be identified and exploited in an optimal way for therapeutic purposes.
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PMID:[Are convulsions necessary for the antidepressive effect of electroconvulsive therapy: outcome of repeated transcranial magnetic stimulation]. 933 58


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