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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic bipolar electrodes were implanted in cortical, limbic, diencephalic and mesencephalic regions of the rat. Following recovery from surgery the rats were maintained for 14--26 days on a liquid diet in which 35--42% of total calories were provided by ethanol. Following ethanol withdrawal, electrographic and behavioral monitoring was continued for 8--10 h. The withdrawal of ethanol resulted in the time-dependent appearance of a variety of withdrawal signs including tail arching, ataxia, rigidity, tremor and spontaneous and audiogenic convulsions. These behavioral signs were accompanied by the development of epileptiform abnormalities across wide-spread brain regions. Analysis of preconvulsive spike activity revealed a greater spike frequency in limbic, mesencephalic and non-specific diencephalic regions, as compared to those in cortex and specific diencephalon. Seizure discharge during the tonic-clonic phase of the primary audiogenic convulsion was initiated in the mesencephalon or amygdala, but spread rather extensively to the remainder of the brain. In those instances, however, where multiple convulsions occurred following the audiogenic convulsions, there was a marked decline in spread of seizure discharge to the cortex. These results were interpreted to support the notion that some degree of neuroanatomical specificity exists in the genesis of epileptiform abnormalities during ethanol withdrawal. A comparison of these results with those studying the neural mechanisms underlying other forms of generalized epilepsy was made. It is hypothesized that central pacemaking regions such as medial thalamus or reticular formation may serve to organize isolated epileptiform activity into coherent patterns of paroxysmal activity throughout the brain during the ethanol withdrawal syndrome.
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PMID:Ethanol dependence in the rat: role of non-specific and limbic regions in the withdrawal reaction. 8 50

Ethanol (3 g/kg, given i.p. as a 33% w/v solution), was given to adult Wistar rats 1 min after training in (1) a 50-trial session of shuttle avoidance, using buzzers and shocks, and (2) an inhibitory avoidance experience in a step-through apparatus. The animals were retested 7 days after training in condition (1), and 3 days after training in condition (2). There was no difference in retention scores between the ethanol-treated, saline-treated, or untreated animals. In addition, there was no evidence of an aversive effect of ethanol per se under any of the two training conditions, in spite of the fact that the dose of ethanol used caused a very profound ataxia, and was lethal for 14.3% of the animals (a slightly higher dose, 4 g/kg, is lethal for about 80% of our rats). These data do not favor the hypothesis that an acute administration of ethanol may influence memory consolidation.
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PMID:A near-lethal dose of ethanol, given intraperitoneally, does not affect memory consolidation of two different avoidance tasks. 10 Aug 17

Two sets of observations are reported as illustrations of problems encountered in behavioral toxicology. First, in an attempt to determine the contribution of methylmercury-induced ataxia to behavioral changes observed on the fixed-consecutive-number schedule, some ancillary control experiments were undertaken. Neither pharmacologically-produced incoordination (ethanol) nor mechanically-produced incoordination (foot taping) led to behavioral changes similar to those seen after exposure to methylmercury. Second, total crop impaction in a pigeon that died during a behavioral experiment on lead suggested some further work. Lead-induced crop stasis in pigeons was measured by x-raying the passage of force-fed stainless steel ball bearings through the crop. This retardation of motility reliably preceded signs of overt toxicity. These results suggest that the behavioral changes in the pigeon noted by us and reported by other investigators cannot be attributed to CNS dysfunction alone, but more likely arise from starvation, or from combined CNS damage and starvation. In addition, these results demonstrate that the appearance of behavioral effects prior to overt toxicity does not necessarily reflect CNS damage.
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PMID:Some problems in interpreting the behavioral effects of lead and methylmercury. 29 71

Mice were placed on an immunization schedule known to result in the production of antibodies directed against a variety of barbiturates (antibody binding capacity = 2.71 pmole 3H-phenobarbital bound/ml undiluted serum). The pharmacologic response to barbiturate in these actively immunized mice and suitably treated controls was investigates using rotarod apparatus for monitoring CNS depression. It was found that the response to pentobarbital in actively immunized mice was decreased, as reflected by an increase in the time the mice remained on the rotarod and a shift of the dose--response curve to the right. The decreased pharmacologic response to pentobarbital was not the result of changes in levels of the hepatic drug metabolism components. Furthermore, the alteration of pharmacologic response in actively immunized mice was selective for barbiturate and did not modify the ataxia produced by administration of another depressant agent, ethanol.
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PMID:Pharmacologic response to pentobarbital in actively immunized mice. 40 75

Rabbits were actively immunized using a barbiturate--BGG conjugate as the immunogen. The antiserum obtained from actively immunized rabbits was administered intravenously to mice to accomplish passive immunization. The antibody binding capacity for 3H-phenobarbital was shown to be sustained in passively immunized mice for periods of up to three weeks. Serum levels of 3H-phenobarbital in passively immunized mice and control mice were compared following drug administration and found to be altered in the antibody-containing mice. There was a 4-fold higher amount of 3H-phenobarbital present in the serum of passively immunized mice compared to control animals. The higher barbiturate levels were due to binding of 3H-phenobarbital to globulin fraction of serum in passively immunized mice. Additionally, decreased pentobarbital-induced ataxia was demonstrated in passively immunized mice. The decreased responsiveness was selective for barbiturates in passively immunized mice and did not modify the ataxia produced in these animals by another depressant agent, ethanol.
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PMID:Pharmacologic response to pentobarbital in passively immunized mice. 43 35

In order to assess the contribution of cerebellar effects of ethanol to the production of ataxia, "nervous" (nr/nr) and control (nr/+ or +/+) C3H mice were tested for locomotor ability 2 min after being given intraperitoneal ethanol injections. The nr/nr mice suffer from loss of most of their cerebellar Purkinje cells. Two doses of ethanol were used: 1.4 or 1.8 g/kg. There were three tests of locomotor ability: holding onto a tilting edge, grid walking, and Rota-rod (treadmill) walking. The result sindicate a primarily additive effect of ethanol and cerebellar pathology in the production of ataxia. The probable mechanism of this additive effect is the transient elimination of Purkinje cell activity following an ethanol injection.
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PMID:Additive effects of ethanol and Purkinje cell loss in the production of ataxia in mice. 82 30

Rats were treated by intragastric intubation of a 20% ethanol solution in doses of 9-15 g/kg in 3-5 fractions for 1-7 days. Both tolerance and physical dependence were demonstrated after this treatment with the maximum tolerable doses to only a few days. Tolerance was assessed by signs of severity of intoxication: coma, loss of righting reflex, ataxia-3, ataxia-2, ataxia-1, sedation, and neutrality. During withdrawal, as blood ethanol concentrations approached 100 mg/dl the ethanol dependence phase was characterized by the onset of signs and responses of progressive severity: hyperactivity, tremors, spastic rigidity, and spontaneous convulsive seizures. A significant degree of tolerance was demonstrated for all signs of intoxication after 4 days of treatment, but did not reach maximum level even after 7 days. The severity of the withdrawal reactions intensified progressively to a maximum intensity after 4 days of treatment when as many as 72% of animals exhibited severe withdrawal signs and reactions including convulsive seizures. These different time courses suggest that tolerance and physical dependence are mediated through different mechanisms.
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PMID:Temporal relationship of the induction of tolerance and physical dependence after continuous intoxication with maximum tolerable doses of ethanol in rats. 82 49

This paper reports findings relative to a simple, rapid and reproducible technique for the induction of physical dependence upon ethanol in the rat. The dependence was induced by intragastric intubation of 20% (w/v) ethanol solutions at 9-15 g/kg in 3-5 fractional doses daily for 4 days, maintaining blood ethanol concentrations above a threshold level sufficient to sustain observable sedation throughout the entire period of intubation. Two phases were distinguished during the withdrawal period: 1. Prodromal detoxication, characterized by a spectrum of signs and responses of diminishing severity, related to the decline in blood ethanol concentrations (mg/dl): death, greater than 640; coma, 780-460; loss of righting reflex, 640-400; ataxia 3-1, 570-250; sedation 340-190; neutrality, 220-130; 2. Ethanol dependence, characterized by a spectrum of withdrawal signs and reactions of progressively increasing severity as blood ehtanol concentration approached 100 mg/dl: hyperactivity, tremors, akinesia, spastic rigidity, and induced and spontaneous convulsions. A rapid sucession of two diverse clusters of signs and reactions represents a reversal of the central nervous system function from the extremes of ethanol intoxication (CNS depression) to the extremes of ethanol dependence (CNS hyperexcitability) during the withdrawal period. Both extremes may terminate in death.
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PMID:Induction of physical dependence upon ethanol and the associated behavioral changes in rats. 123 14

Anxiolytic agents disinhibit suppressed behaviors in rodents in preclinical models of anxiety such as the non-conditioned social interaction and elevated plus maze assays and the conditioned conflict Cook and Davidson procedure. The (+) and (-) enantiomers of (+/-)-3-amino-1-hydroxy-2-pyrrolidinone (HA-966) have been resolved and revealed that R-(+)-HA-966 significantly disinhibits both non-conditioned and conditioned suppressed behavior similar to the benzodiazepine diazepam, while the S-(-) enantiomer was devoid of anxiolytic activity and only produced behavioral sedation. Furthermore, R-(+)-HA-966 lacked side-effects in rodents commonly associated with the administration of benzodiazepines such as motor incoordination and ataxia, significant interactions with ethanol, and amnesia. These data suggest that R-(+)-HA-966, an antagonist at the strychnine-insensitive glycine/NMDA receptor site, was anxioselective and lacked some of the side-effects associated with benzodiazepine anxiolytics.
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PMID:Stereoselective R-(+) enantiomer of HA-966 displays anxiolytic effects in rodents. 135 34

Phencyclidine (PCP), a drug inducing schizophrenia-like symptoms in humans, is reported to be a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors. In rats, PCP produces three dose-dependent stages of EEG patterns: 1) increase of cortical desynchronization duration; 2) increase of the amplitude of the high-frequency (20-30 Hz) low-voltage (30-50 microV) cortical background activity; 3) appearance of cortical slow (2-3 Hz) wave-sharp wave complexes. These EEG changes are accompanied by stimulatory-depressive effects such as stereotypy (circling, head weaving) and ataxia. In the present study, the EEG and behavioural effects induced by systemic administration of the NMDA antagonists dizocilpine (MK 801), dextromethorphan (DM), [(+)-alpha-(4-chlorophenyl)-4- [(phenyl)methyl-1-piperidine ethanol] (SL 82.0715), (+)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755) have been compared to those of PCP in rats. The rank of potency for inducing PCP-like EEG stages 1-3 was as follows: MK 801 > PCP > CGS 19755 > CPP. These drugs also induced PCP-like behavioural effects. On the contrary, DM and SL 82.0715, administered up to the dose of 100 mg/kg IP, failed to induce PCP-like behavioural effects and elicited only the stage 1 of PCP-like EEG. These results strongly suggest the involvement of NMDA neurotransmission in the behavioral and EEG effects of PCP.
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PMID:Different capability of N-methyl-D-aspartate antagonists to elicit EEG and behavioural phencyclidine-like effects in rats. 136 27


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