Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-three drug abusers and seventeen controls underwent clinical neurological examinations and magnetic resonance imaging (MRI) of the brain. The drug abuse encompassed cannabis, inhalants, opiates, psychedelics, amphetamines, and cocaine but not necessarily all drugs in all persons. The drug abuse was always combined with heavy alcohol consumption. One drug abuser had abnormal neurological findings which consisted of lower limb ataxia and 3 others had mild imbalance. MRI examinations did not show differences in width of the third, fourth or lateral ventricles nor the diameter of the cerebral aqueduct but the drug abusers had significantly smaller vermes cerebelli compared to controls. White matter changes also occurred more often in the drug abuser group. These findings are not consistent with known side-effects of the narcotic drugs but more probably a result of very high alcohol consumptions in parallel with drug abuse. Alcohol is clearly a much more potent brain toxic agent than are the most commonly abused narcotic drugs.
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PMID:Minor structural brain changes in young drug abusers. A magnetic resonance study. 847 92

The monosialoganglioside, GM1, protects the nervous system against a variety of insults. In this study, we evaluated the protective properties of GM1 on ethanol intoxication and development of dependence. GM1 (20-40 mg/kg, IP) reduced the extent and duration of ataxia produced by ethanol (2 g/kg, IP, 15-95 min), and delayed the onset of loss and reduced the duration of the righting reflex (LORR) produced by ethanol (4.2 g/kg, IP). GM1 did not alter ethanol-induced hypothermia or the rate of ethanol clearance. Rather, GM1 increased the waking blood ethanol concentration. In animals fed a complete liquid diet containing 4.5% ethanol, concurrent administration of GM1 (40 mg/kg/day) blocked the tremors, hypolocomotion, and anxiety-like behavior associated with ethanol withdrawal. These findings demonstrate that GM1 reduces both ethanol's acute intoxication and the signs and symptoms of ethanol withdrawal by a mechanism not related to ethanol pharmacokinetics.
Alcohol
PMID:GM1 ganglioside reduces ethanol intoxication and the development of ethanol dependence. 859 Jun 22

Rapid tolerance to rotarod ataxia has previously been demonstrated in mice after sequential ethanol injections. Here we tested DBA/2J and C57BL/6J mice for initial ethanol sensitivity; DBA/2J mice were more sensitive (0.40 +/- 0.17 mg/g brain) than C57BL/6J mice (1.44 +/- 0.12 mg/g). We then monitored the development of tolerance by quantifying blood ethanol concentrations at the recovery from ataxia over five sequential injections; tolerance reached a plateau in about 5 hr. DBA/2J mice became very tolerant (final ethanol threshold 3.47 +/- 0.16 mg/ml, an increase of 3.07 mg/ml, or 8.7-fold above base line); B6 became slightly tolerant (final ethanol threshold 2.62 +/- 12 mg/ml, and increase of 1.18, or 1.8-fold above base line). Therefore, by the end of the treatment regimen, the rank order of sensitivity of the two strains had reversed. We then tested 25 recombinant inbred strains from among strains representing a cross between C57BL/6J and DBA/2J inbred strains, followed by a quantitative trait locus analysis with a database of 1522 markers to identify provisional loci. This procedure identified 19 markers on 11 chromosomes for initial sensitivity, 18 markers on 9 chromosomes for tolerance (delta) and 21 markers on 11 chromosomes for tolerance (fold-increase). Of these, 17 markers were in common, which suggests that initial sensitivity and tolerance share substantial genetic codetermination. Major candidate loci will be confirmed by genotyping B6D2F2 offspring that have been tested for initial sensitivity and tolerance.
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PMID:Identification of genetic markers for initial sensitivity and rapid tolerance to ethanol-induced ataxia using quantitative trait locus analysis in BXD recombinant inbred mice. 862 37

Ethanol (EtOH) has both locomotor stimulant and locomotor ataxic effects. Repeated EtOH treatment can result in the development of behavioral sensitization (increased sensitivity) similar to that seen with the classical stimulant drugs amphetamine and cocaine. However, it has been suggested for EtOH that sensitization may be a by-product of the development of tolerance to the sedative/ataxic effects of EtOH. It is also possible that the converse is true: that tolerance develops as the result of sensitization development. We examined this notion by measuring EtOH sensitization and tolerance in the BXD/Ty recombinant inbred strains. Changes in locomotor activation and grid test ataxia were used as the measures of sensitization and tolerance, respectively. If a genetic relationship exists between sensitization and tolerance, then those strains most susceptible to sensitization should also develop the most robust tolerance. Genetic correlations did not support the presence of this relationship. In addition, the use of the BXD/Ty recombinant inbred strains enabled us to perform gene mapping by quantitative trait locus analysis for activity and ataxia measures. We found that 28% to 79% of the genetic variation in the various activity and ataxia responses could be explained by the identified quantitative trait loci associations. However, when associations of gene markers with behavioral phenotypes were compared, we obtained no strong evidence for common genes determining magnitude of sensitization and tolerance. Thus the results of this study do not support the hypothesis that sensitization results from development of tolerance to the sedative/ataxic effects of EtOH or, conversely, that tolerance is a by-product of sensitization.
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PMID:Evaluation of potential genetic associations between ethanol tolerance and sensitization in BXD/Ty recombinant inbred mice. 862 38

Sensitivity and tolerance to ethanol-induced ataxia and hypothermia are determined in part by genetic factors; some genes that affect one of these traits may affect others as well. To test this general hypothesis, we examined hypothermia and two tests of ataxia in the C57BL/6J and DBA/2J inbred mouse stains and in 18 to 25 of their recombinant inbred strains. Genetic correlations among strain mean responses revealed strong positive associations of genetic origin between sensitivity and tolerance for each of the three responses. Furthermore, tolerance to grid test ataxia and tolerance to hypothermia were positively associated. Sensitivity scores across the three responses were uncorrelated. The second method employed to assess genetic correlation was to examine the pattern of genetic locations of quantitative trait loci (QTLs) provisionally identified using genetic mapping procedures. This method identified 3 to 14 QTLs associated with each trait. Within each response, a number of these associations were in common for measures of sensitivity and tolerance; this suggests the existence of several specific genes that exert pleiotropic effects on sensitivity and tolerance. In a result consistent with the analyses of genetic correlations, there was modest evidence for QTLs associated across measures. Some QTLs associated with multiple traits mapped to chromosomal regions where candidate genes (e.g., genes for neurotransmitter receptors) have been mapped. In summary, the analyses presented suggest modest commonality of genetic influence on tolerance to some measures of ataxia and hypothermia, and they strongly support previous data indicating that sensitivity and tolerance to specific effects of ethanol share common genetic determinants.
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PMID:Common genetic determinants of the ataxic and hypothermic effects of ethanol in BXD/Ty recombinant inbred mice: genetic correlations and quantitative trait loci. 862 39

This study describes the development and characterization of a binge drinking model in which a single dose of ethanol (EtOH) is administered by gavage to B6C3F1 mice. Blood EtOH levels were monitored over time after administration of EtOH at doses of 3.0-7.0 g/kg. Peak levels were in the range of 0.2-0.5%, and clearance was complete within 2-12 hr. Substantial increases in blood corticosterone levels were noted. Behavioral changes in EtOH-treated mice aged 8 weeks ranged from no effect (3-4 g/kg) to severe ataxia (6-7 g/kg). In mice aged 16 weeks, a dosage of 7 g/kg caused less of the righting reflex in some animals and severe ataxia in most of the others. Clinical chemistry results did not indicate biologically important changes in general physiological/homeostatic systems in EtOH-treated mice, but there were indications of minor liver damage at the 7 g/kg dosage. Thus, administration of EtOH to B6C3F1 mice by gavage produces behavioral changes, changes in blood EtOH levels, and probably glucocorticoid levels representative of at least some human binge drinkers. The model was used to evaluate the effects of binge drinking on antibody responses, and the results indicate the model will be useful for such studies.
Alcohol Clin Exp Res 1996 Feb
PMID:Development and characterization of a binge drinking model in mice for evaluation of the immunological effects of ethanol. 865 42

Ataxia, sedation, amnesia, ethanol and barbiturate potentiation, tolerance, dependence, and the potential for drug abuse plague the clinical use of anxiolytic benzodiazepines. Benzodiazepine and non-benzodiazepine ligands that are in current clinical use act as full allosteric modulators of GABA-gated Cl- channels, and on chronic administration trigger compensatory changes in the subunit expression of GABAA receptors. In these putative abnormal receptors, full allosteric modulators have low intrinsic activity and potency, and tolerance and dependence ensue. In this review, Erminio Costa and Alessandro Guidotti discuss the development of partial allosteric modulators, such as imidazenil, which have high potency and low intrinsic activity at GABA-gated Cl- channels. Since in animals tolerant to full allosteric modulators imidazenil also fails to show cross-tolerance, it is an example of a new type of anxiolytic and anticonvulsant drug acting at GABAA receptors via benzodiazepine recognition sites.
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PMID:Benzodiazepines on trial: a research strategy for their rehabilitation. 866 26

Rats were administered either 80 escapable shocks or yoked inescapable shocks, were then injected with saline or several ataxic doses of either ethanol or midazolam, and then had their motoric impairment assessed by Rotarod performance. No motoric impairment was observed following saline injection. However, inescapable shock impaired Rotarod performance in response to both ethanol and midazolam at 2 hr, but not immediately poststress. Conversely, escapable shock reduced the ataxic potency of ethanol, although it had no influence on midazolam-induced ataxia. These results indicate functional alterations in behavioral reactivity to low doses of several classes of central nervous system depressants by psychological dynamics of stress exposure. Our findings demonstrate the impact of stress controllability on behavioral reactivity to two classes of drugs of abuse.
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PMID:Stress controllability influences the ataxic properties of both ethanol and midazolam in the rat. 873 Oct 63

Substantial evidence links alcohol drinking and serotonin (5-HT) functioning in animals. Lowered central 5-HT neurotransmission has been found in a subgroup of alcoholics, possibly those with more aggressive, assaultive tendencies. Several rodent studies have also suggested that intact 5-HT systems are important determinants of sensitivity and/or tolerance to ethanol-induced ataxia and hypothermia. Null mutant mice lacking the 5-HT1B receptor gene (5-HT1B-/-) have been developed that display enhanced aggression and altered 5-HT release in slice preparations from some, but not all, brain areas. We characterized these mice for sensitivity to several effects of ethanol. Mutant mice drank twice as much ethanol as wild-type mice, and voluntarily ingested solutions containing up to 20% ethanol in water. Their intake of food and water, and of sucrose, saccharin and quinine solutions, was normal. Mutants were less sensitive than wild-types on a test of ethanol-induced ataxia and, with repeated drug administration, tended to develop tolerance more slowly. In tests of ethanol withdrawal and metabolism, mutants and wild-type mice showed equivalent responses. Our results suggest that the 5-HT1B receptor participates in the regulation of ethanol drinking, and demonstrate that serotonergic manipulations lead to reduced responsiveness to certain ataxic effects of ethanol without affecting dependence.
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PMID:Elevated alcohol consumption in null mutant mice lacking 5-HT1B serotonin receptors. 878 28

Mechanism of essential tremor remains unknown. Central oscillators, postulated in thalamus, inferior olive, and spinal cord are thought to be important to form rhythmicity, and finally to stimulate spinal or medullary motor cells, leading trembling muscle contraction, tremor. Among several subtypes of essential familial tremor, including hand tremor, neck tremor, and voice tremor, essential neck tremor is a common disorder, and its pathophysiology seems different from that of typical essential hand tremor, since patients with essential hand tremor are responsive to beta blocker, whereas those with neck tremor are usually not. We experienced a 41-year-old left handed woman with essential neck tremor in whom neck titubation disappeared shortly after pontine base infarct. She was our patient in the outpatient clinic with the diagnosis of essential neck tremor. The tremor developed when she was teenage, and has been localized in the neck muscles. Alcohol intake had apparently diminished it transiently. Her mother also had the tremor in her neck. She was admitted to our hospital with sudden onset of right-sided limb weakness and speech disturbance. Neurological examination showed right hemiparesis including the ipsilateral face, scanning speech, and cerebellar limb ataxia on the same side. In addition, there was no tremor in her neck. Brain MR imaging revealed a pontine base infarct at the level of middle pons, which was consistent with paramedian artery territory. The hemiparesis and speech disturbance improved almost completely after treatment, and her neck tremor has never occurred in one year follow-up. In our patient, efficacy of alcohol imply that essential neck tremor and hand tremor had same central nervous pathway including central oscillator in common, and descending cortical fibers is seemingly associated with diminishing patient's tremor. Pathophysiology of essential neck tremor was discussed with reviewing previous literature.
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PMID:[Disappearance of essential neck tremor after pontine base infarction]. 879 10


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