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)

To test the effect of inhibiting serotonin uptake on voluntary alcohol intake, 20 alcohol-dependent males were housed on a locked hospital ward with 60-ml drinks of 97.5 proof alcohol available in a fixed interval drinking decision paradigm 13 times each day. After a 3-day, single-blind placebo baseline period, 10 subjects each received the serotonin uptake blocker fluoxetine (up to 80 mg po daily) or placebo double-blind for 28 days. The fluoxetine group had a 14% lower alcohol intake during the 1st week only, associated with a lower proportion of requests for alcohol and less craving for alcohol (as rated by research staff). There were no significant effects in later weeks, nor any differences in scores on the Hamilton Depression and Anxiety Scales or the Hopkins Symptom Checklist.
Alcohol Clin Exp Res 1992 Apr
PMID:Effect of fluoxetine on alcohol consumption in male alcoholics. 131 33

Seventy-five alcohol-dependent patients (35 males, 40 females) treated by a Minnesota Model in-patient programme were followed up for 1 year. A variety of outcome measures were included, and patients' GPs were also questioned with regard to various aspects of their involvement in treatment for alcohol problems. Males admitted to the programme had a longer history of drinking, consumed more alcohol and showed greater expenditure on alcohol. At 6 months, 66% of males and 45% of females were abstinent; at 1 year, the proportions abstinent were 53% and 39%, respectively. Good outcome for both sexes was associated with attendance of Alcoholics Anonymous meetings. Poor outcome at 1 year was associated with a lack of GP involvement in aftercare and failure to provide alcohol counselling in the community. Females appeared to be particularly disadvantaged by depressive comorbidity. Males showed poorer outcome if they belonged to social class IIIM or lower, were unemployed, or had a family history of alcoholism. It is suggested that closer attention should be paid to monitoring patients' mood state, with appropriate treatment of depression, and that GPs need on-going support and education for helping patients with alcohol problems.
Alcohol Alcohol 1992 Jul
PMID:In-patient treatment of alcohol problems--predicting and preventing relapse. 132 88

1. Intracellular recordings were made from pyramidal cells in area CA1 in mouse isolated hippocampal slices, after chronic ethanol treatment in vivo. 2. Fast i.p.s.ps were isolated by injection of the impaled neurones with QX314 (to block fast sodium currents and the slow i.p.s.p.) and stimulating the interneurones in the presence of the glutamatergic blockers, CNQX and APV. 3. The isolated fast-inhibitory postsynaptic potential (f.-i.p.s.p.) was measured at intervals during the 7 h withdrawal period. The reversal potential and sensitivity to bicuculline suggested that the isolated f.-i.p.s.p. was mediated by activation of the GABAA receptor-chloride ionophore complex. 4. Measurement of stimulus-response relationships for the f.-i.p.s.ps revealed an initial increase in the maximum size of the i.p.s.p., evoked from a membrane potential of -50 mV, seen at 2 h into ethanol withdrawal. This was attributed to a negative shift in the reversal potential, Ei.p.s.p., with no observed change in conductance, Gi.p.s.p. 5. No differences in f.-i.p.s.ps evoked during ethanol withdrawal or in control slices were seen at 4 h or 6 h. At these times, epileptiform activity was seen in previous field potential recordings. 6. Paired pulse depression of the f.-i.p.s.p. was significantly increased at 2 h into withdrawal, when a 150 ms pulse interval was used. No differences were seen at later times in the ethanol withdrawal period. 7. The results suggest that ethanol withdrawal hyperexcitability in isolated hippocampal slices is not caused by primary decreases in inhibition mediated by the GABAA receptor-chloride ionophore complex.4. Measurement of stimulus-response relationships for the f.-i.p.s.ps revealed an initial increase in the maximum size of the i.p.s.p., evoked from a membrane potential of - 50 mV, seen at 2 h into ethanol withdrawal. This was attributed to a negative shift in the reversal potential, Ejp.sp with no observed change in conductance, Gj ps p.5. No differences in f.-i.p.s.ps evoked during ethanol withdrawal or in control slices were seen at 4 h or 6 h. At these times, epileptiform activity was seen in previous field potential recordings.6. Paired pulse depression of the f.-i.p.s.p. was significantly increased at 2 h into withdrawal, when a 150 ms pulse interval was used. No differences were seen at later times in the ethanol withdrawal period.7. The results suggest that ethanol withdrawal hyperexcitability in isolated hippocampal slices is not caused by primary decreases in inhibition mediated by the GABAA receptor-chloride ionophore complex.The increase in the f.-i.p.s.p. during the initial stages of the withdrawal might prevent the overt expression of epileptiform activity at this time.
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PMID:Changes in intrinsic inhibition in isolated hippocampal slices during ethanol withdrawal; lack of correlation with withdrawal hyperexcitability. 133 Jan 82

Acute ethanol influence on field L auditory evoked potentials (AEP) was studied in 4-8-days-old altricial nestlings of pied flycatcher. Nestlings were presented with tone pips related with the realization of natural behaviour (2.0 and 5.0 kHz) and bearing no meaning for the behaviour of the young of the age under study (3.0 kHz). Ethanol ingestion was found to reduce the maturity index (MI) of AEP in response to "behavioural" but not to control frequencies; this effect was first observed at day 5, when nestlings eyes opened and defence behaviour appeared, while previously formed feeding behaviour was significantly modified. During the next 2 days alcohol had a greater effect upon the AEP in response to 2.0 kHz tone pips, related with feeding behaviour of increasing complexity than upon the AEP in response to 5.0 kHz, related with the defence behaviour that remained relatively constant. The previous data concerning the effect of alcohol on unit activity are used to support the view that MI increase during the early postembryonic ontogeny is due to the involvement of neurons with newly formed behavioural specializations into the subserving of new behavioural patterns while the decrease of MI under alcohol is due to the depression of activity in these neurons.
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PMID:[The effect of acute alcohol administration on auditory evoked potentials in altricial nestlings during the development of natural behavior]. 133

Coccinia indica (Family: Cucurbitaceae, locally known as telakucha) leaves were extracted with 95% ethanol. Following evaporation of the solvents, the residue was suspended in distilled water. When this suspension was fed orally to male normal-fed and 48-hr starved rats, the blood glucose was lowered 21% (P less than 0.01) in normal-fed and 24% (P less than 0.001) in 48-hr starved animals respectively. Starvation had induced a 3-fold increase in the activity of glucose-6-phosphatase and this activity was depressed 19% (P less than 0.05) by extract feeding while basal activity of the enzyme in normal-fed rats remained unaffected. Consistent with the depression of glucose-6-phosphatase, urea cycle enzyme arginase was also depressed 21% (P less than 0.001) and 12% (P less than 0.01) in the liver of 48 hr-starved and normal-fed animals respectively. Unlike glucose-6-phosphatase, starvation induced levels of gluconeogenic enzymes alanine aminotransferase and aspartate aminotransferase were not affected by Coccinia extract. These results suggest that the hypoglycemic effect of C. indica is partly due to the repression of the key gluconeogenic enzyme glucose-6-phosphatase.
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PMID:Hypoglycemic effects of Coccinia indica: inhibition of key gluconeogenic enzyme, glucose-6-phosphatase. 133 43

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.
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PMID:5-Hydroxytryptamine3-receptor blockade protects against gastric mucosal damage in rats. 134 85

Drug-induced depression which is classified as DSM-III-R is difficult for clinicians to diagnose because the cause is not easily distinguishable from adjustment disorders or nonorganic mood disorders. This review summarizes the few articles published within 20 years as searched in the Index Medicus about the clinical manifestations of organic mood syndromes from oral contraceptives (OCs), beta blockers, alcohol and sedative-hypnotic drugs, and other medications. There was a noticeable lack of articles and specific clinical features which would help differentiate causes. Oral contraception may cause depression by inducing hepatic tryptophan oxidase, which may lead to a deficiency of vitamin B6. The most common reason for discontinuing OCs is depression, i.e., there are reports of a rate of 70/1000 woman years during the 1st year of OC use. However, the rate among females examined in a catchment study was similar at 6.6%. There is some indication that depression may be dose related, i.e., low dose is related to the same prevalence as in the control group. A basic requirement of DSM-III-R is severe and persistent depression; OC-related depression does not exhibit sleep or appetite disturbances. The relationship between beta blockers and depression indicates that the prevalence and the nature of the relationship are not consistently confirmed. Depressive episodes (14) reported in 8 studies showed major depression and suicidal thoughts or attempts just after initiation of propranolol and resolution when the drug was discontinued; timing of the symptoms may be the best basis upon which to make a clinical judgement. Alcohol use is usually seen as associated with depression, but the extent to which alcohol induces depression is unknown. Symptoms are transitory and appear during bouts of heavy drinking. Studies on benzodiazepine use and depression are reported to be confounded by other factors. Other depression-causing agents for which information was unavailable are identified as psychostimulants, metoclopramide, H-2 blockers, methyldopa, and steroids.
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PMID:Can drug-induced depressions be identified by their clinical features? 135 May 3

The evidence presented above indicates that GABA- and glutamate-activated ion channels are molecular sites of alcohol and anesthetic action. In view of the important role that these channels play in CNS excitability, it seems likely that the actions of alcohol and anesthetics on these channels contribute significantly to the behavioral effects of these agents. Although the behavioral effects of alcohol and anesthetics may well result from a combination of actions on different ion channels and other molecular sites in the CNS, it is of interest to consider whether the actions of these agents on particular types of ion channels may contribute to particular behavioral effects. In this regard, it should be noted that benzodiazepines potentiate GABAA responses, but do not produce intoxication or general anesthesia in their clinical dose range. Benzodiazepines are widely used clinically, primarily for their anxiolytic actions (26), suggesting that the potentiation of GABAA responses by ethanol and barbiturates may contribute to the anxiolytic effects of these agents. Since kainate and quisqualate channels mediate fast excitatory transmission in the CNS, inhibition of kainate and quisqualate receptor-activated responses would be expected to result in general CNS depression. This suggests that inhibition of kainate and quisqualate receptor-mediated responses may contribute to the general anesthetic effects of ethanol, trichloroethanol and barbiturates. NMDA channels are thought to mediate complex excitatory neural phenomena and cognitive function. In view of this, the observation that ethanol inhibits NMDA receptor-mediated responses over the concentration range that produces intoxication and the correlation between the potency of different alcohols for inhibiting NMDA-activated current and their potency for producing intoxication suggest that ethanol-induced inhibition of NMDA receptor-mediated responses may contribute to the intoxicating effects of ethanol. Although these speculations are no doubt oversimplifications, the recognition that GABA- and glutamate-gated ion channels are molecular sites of alcohol and anesthetic action provides a basis for investigating the molecular mechanisms involved in the action of these agents and the behavioral significance of those actions.
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PMID:GABA- and glutamate-gated ion channels as molecular sites of alcohol and anesthetic action. 135 18

Male Swiss-Webster mice were used to examine the effect of NMDA on the ethanol-induced loss of the righting reflex (LORR). The LORR was used as a measure of CNS depression. Immediately after animals regained the righting reflex following ethanol injection (4.0 g/kg, IP) mice received an ICV injection of saline or NMDA (10, 50, 100, or 500 nmol/kg) in a volume of 5 microliters. Upon ICV injection of NMDA, mice again lost the righting reflex and this effect of NMDA in the presence of ethanol occurred rapidly and in a dose-dependent manner. In another experiment DL-2-amino-5-phosphonovaleric acid (APV), a competitive antagonist of NMDA, was given ICV with NMDA (50 nmol/kg) in the presence of ethanol. APV (10 and 100 nmol/kg, ICV) significantly attenuated the response of NMDA to enhance the depressant action of ethanol. When bicuculline methiodide, an antagonist of GABA, was given ICV with NMDA (50 nmol/kg), bicuculline methiodide reduced the effect of NMDA to produce a second loss of the righting reflex (return to the LORR) in the presence of ethanol. When NMDA (100 nmol/kg, ICV) was injected in the absence of ethanol into mice, NMDA by itself did not produce a loss of the righting reflex. In this investigation, the results suggest that NMDA can augment ethanol-induced depression possibly through an interaction between glutamatergic and GABAergeric systems in the CNS.
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PMID:NMDA enhances the central depressant properties of ethanol in mice. 135 77

The benzodiazepine antagonist flumazenil is a very valuable tool in the diagnosis and treatment of intoxications in which benzodiazepines are involved. In case of a positive response, patients will regain consciousness immediately, thus verifying the diagnosis and making a brief history possible to identify other drugs that might be involved. Moreover, invasive diagnostic and therapeutic procedures like gastric lavage, lumbar puncture, mechanical ventilation, etc., may then be unnecessary. In cases of pure benzodiazepine overdose a single injection of flumazenil 0.2mg should be given, followed by individually titrated increments of 0.1 mg/min until the patient is awake and responsive. In these cases a total dose of 2mg is usually sufficient. Higher doses of flumazenil may be necessary in cases of combined drug overdose. Because of its high therapeutic index, the administration of flumazenil is usually not accompanied by serious adverse effects. Benzodiazepine withdrawal syndromes characterised by transient anxiety and depression can occur, but the incidence is low. Increases of blood pressure and heart rate due to a release of catecholamines are possible, which might endanger patients with cardiovascular diseases. In severe cases, seizures have been observed which usually respond well to small doses of benzodiazepine agonists. In all cases of successful treatment it should be remembered that the effect of flumazenil deteriorates after 1 to 2h, which usually leads at first to resedation. In these patients additional bolus injections or a continuous infusion (0.1 to 0.5 mg/h) may be necessary. The effectiveness of flumazenil in cases of alcohol (ethanol) poisoning is questionable and should be further investigated.
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PMID:Benzodiazepine antagonists. An update of their role in the emergency care of overdose patients. 135 15


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