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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous problems have been associated with previous attempts to develop a suitable method for the induction and assessment of alcohol dependence and withdrawal syndrome in the rat. Using our modification of a common inhalation method for the long-term administration of ethanol, these problems can be eliminated. Adult male rats (Long Evans and Brattleboro) were exposed to ethanol vapor concentrations of 7 to 35 mg/liter of air, which cause rapid development of tolerance and physical dependence. With this inhalation method, it is possible to obtain and easily maintain high levels of ethanol in the blood (150 to 400 mg/dl). When exposure to ethanol is terminated, ethanol is eliminated from the system within 1 to 6 hr. This rapid elimination of ethanol is accompanied by a high susceptibility to withdrawal reactions. The severity of the withdrawal syndrome was assessed within 6 to 24 hr after cessation of the ethanol administration by exposing each rat individually to a 60 to 120-sec period of bell ringing. Convulsive seizures were observed in nearly 90% of the animals tested, with a mortality rate of less than 20%.
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PMID:Alcohol dependence and withdrawal in the rat. An effective means of induction and assessment. 371 3

The continuous infusion of 45 mg/kg/24 hr of phencyclidine (PCP) into the jugular vein of unrestrained rats induced tolerance to PCP-induced impairment of forced motor activity and physical dependence in 3.5 and 7 days, respectively. In drug-naive rats, an i.v. 2-mg/kg PCP test dose abolished rotarod performance for more than 20 min which returned to pretreatment values at 40 min. Eight hours after the termination of 3.5 days of infusion, rotarod performance of PCP-infused rats was significantly less impaired by the PCP test dose at 20 min than that of saline-infused controls. After infusion of PCP for 7 days, the duration of performance abolition produced by the PCP test dose (given 8 hr after the termination of infusion) was shortened further with performance significantly better than that of saline-infused controls at both 10 and 20 min. The results showed a greater than 2-fold tolerance development to this PCP effect and suggest the observed tolerance to be mainly functional in nature. Abrupt withdrawal of PCP after infusion for 7 days resulted in an abstinence syndrome with the following signs: piloerection, increased susceptibility to audiogenic seizures, transient weight loss and reductions in exploratory activity and rotarod performance. The first withdrawal signs were noted 4 hr after the termination of infusion. At 24 hr of abstinence, most of the withdrawal signs had subsided. The reduced rotarod performance, associated with withdrawal, could be reversed by a single i.v. dose of 2 mg/kg of PCP. The reversibility of this sign supports the interpretation of impaired rotarod performance after withdrawal as being an abstinence sign and adds to the experimental evidence that physical dependence on PCP is inducible within 7 days in rats.
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PMID:Continuous intravenous infusion of phencyclidine in unrestrained rats results in the rapid induction of tolerance and physical dependence. 404 May 69

Rats maintained on an intermittent food schedule with an available ethanol solution drink to excess (13.1 grams of ethanol per kilogram of body weight, daily). Removal of ethanol produces symptoms of physical dependence including death from tonic-clonic seizures. Overindulgence in oral self-administration of an aqueous ethanol solution, resulting in unequivocal physical dependence, approximates a model of human alcoholism.
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PMID:Behavioral maintenance of high concentrations of blood ethanol and physical dependence in the rat. 506 93

1. We have stressed the detrimental effect that lay publications, T. V. and mass media has had on the pharmacotherapy of anxiety and depressive reactions with benzodiazepines. 2. We have reviewed the scientific literature and found few well documented cases of benzodiazepine dependence if one considers that benzodiazepines are the most prescribed medications. 3. We discussed the possibility that the seizures reported on withdrawal of benzodiazepines used for very long periods, is not a "proof" of a physical dependence, but rather clinical evidence of the well known anticonvulsant effect of benzodiazepines. 4. We have hypothesized that the withdrawal syndromes associated to high dosages of benzodiazepines might have a different neurochemical mechanism to that observed in alcohol and barbiturates withdrawals.
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PMID:Long term use and abuse of benzodiazepines. 610 79

Clinical trials have indicated that buspirone (Buspar) is effective in the treatment of anxiety with efficacy and dosage comparable to diazepam. Until recently it has been thought that antianxiety drugs must alter benzodiazepine receptor binding in vitro. However, buspirone lacks any structural similarity to te benzodiazepines and does not interact with the benzodiazepine/gamma-aminobutyric acid (GABA) axis. Specifically, buspirone neither stimulates nor inhibits [3H]benzodiazepine binding, does not affect the influence o GABA or halide anions on benzodiazepine binding, and does not interfere with GABA binding or uptake. Behavioral testing has revealed that buspirone does not produce muscle weakness, does not control seizures, does not potentiate the impairment of psychophysiological function or lethality produced by administration of CNS depressants, does not produce sedation/hypnosis and does not appear to possess any abuse potential or liability for physical dependence. Thus, buspirone has been termed an anxioselective agent. Buspirone appears to only interact with the dopaminergic system with reasonable potency and exhibits properties of both a dopamine agonist and a dopamine antagonist. This suggests that dopamine is implicated in the etiology and expression of anxiety. A discussion of this implication is presented with a review of the clinical efficacy of nonbenzodiazepine drugs, especially dopamine agonists and dopamine antagonists, in the management of anxiety. In addition, neuropharmacological studies which have investigated the role of dopamine in animal models of anxiety are considered. Finally, the multiplicity of dopamine receptors and their regional localization in the brain are considered in the formulation of an hypothesis which features a role for the dopaminergic agents in the pharmacotherapy of anxiety.
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PMID:Dopamine and antianxiety activity. 613 25

Dogs, surgically implanted with a gastric fistula, were chronically dosed with diazepam or lorazepam. Diazepam (60 mg/kg/day) or lorazepam (100 mg/kg/day) was administered intragastrically in four divided daily doses. Beginning no less than 2 weeks after the attainment of stabilization doses, dogs underwent withdrawal experiments, repeated at 2-week intervals. At a time of withdrawal determined by a Latin square crossover design, dogs were observed for 8 hr for signs of abstinence. Both diazepam and lorazepam caused a withdrawal abstinence syndrome to appear upon abrupt discontinuation of the drug. The two abstinence syndromes had many signs in common, including tremor, hot foot walking, rigidity and decreased food intake, but the lorazepam withdrawal abstinence syndrome was much less intense and had a shorter latency to onset than the diazepam abstinence syndrome, which also included clonic and tonic-clonic convulsions and was lethal in two dogs. Furthermore, the diazepam withdrawal abstinence syndrome was biphasic, the first phase apparent by 24 hr and a second phase beginning at 48 hr, whereas the lorazepam syndrome was not. Diazepam suppressed the major signs of diazepam abstinence in a dose-related manner, but failed to completely suppress all signs of abstinence. CGS-8216, a pyrazoloquinoline benzodiazepine antagonist, precipitated abstinence in the diazepam-dependent dog, but did not precipitate tonic-clonic seizures. No abstinence syndrome was precipitated in the lorazepam-dependent dog. These results would suggest that whereas diazepam and lorazepam both cause physical dependence the two syndromes are not the same and, furthermore, that physical dependence on, and withdrawal from, diazepam involves at least two separate mechanisms with different selectivity for benzodiazepine agonists and antagonists.
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PMID:Physical dependence on diazepam and lorazepam in the dog. 613 1

We are selectively breeding mice prone (WSP) and resistant (WSR) to ethanol withdrawal seizures assessed by handling induced convulsions (HIC). The possibility that differences between the lines in HIC scores are a result of differences in general CNS excitability not specific to ethanol withdrawal was examined. Using treatments which produce generalized seizures (electroconvulsive shock, strychnine, and flurothyl) and gamma amino-butyric acid (GABA) antagonists (picrotoxin, bicuculline, and pentylentetrazol), the ED50 for seizures was determined in the selected lines. In addition, the sensitivity of WSP and WSR mice to the anticonvulsant actions of ethanol against each treatment was determined. Neither the convulsant amperage 50 (CA50) for ECS nor the ED50 for any drug treatment differed for the selected lines. When ethanol (1.5 g/kg) was administered prior to ECS, there was a dramatic differential suppression of ECS in the lines: the CA50 of WSR mice was elevated 5-fold, whereas the CA50 of WSP mice increased only two fold. Ethanol pretreatment also elevated the ED50 for strychnine and flurothyl in WSR mice significantly more than WSP mice, but the line difference was smaller than for the anticonvulsant effect against ECS. The ED50s for the GABA antagonists were not different between the WSR and WSP lines after ethanol pretreatment. We conclude that genetic selection is producing lines of mice that differ specifically in the degree of seizure severity caused by withdrawal from ethanol physical dependence and not in generalized CNS excitability. An increased sensitivity to the anticonvulsant effects of ethanol against some convulsant treatments has appeared as a correlated response to selection in the WSR line.
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PMID:Specific ethanol withdrawal seizures in genetically selected mice. 654 39

A relatively simple and rapid method has been developed to induce tolerance to and dependence on alcohol in mice. Alternating intraperitoneal injections of metabolically stable tert-butanol and ethanol for 4 consecutive days resulted in a physical dependence on alcohol, which was quantified by the latency and ED50 of picrotoxin-induced CNS hyperexcitability--myoclonic and tonic seizures and mortality--during the withdrawal period. The data indicate that alcohol-dependent animals in the withdrawal period are more susceptible than alcohol-naive controls to picrotoxin. Withdrawal hyperexcitability can be quantified by the ED50 of picrotoxin.
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PMID:Increased sensitivity to picrotoxin as an index of physical dependence on alcohol in the mouse. 654 88

Genetic selection based on severity of withdrawal seizures following inhalation of ethanol vapor has produced two lines of mice, WSR (withdrawal seizure resistant) and WSP (withdrawal seizure prone), that differ markedly in withdrawal signs. In the present study, we report that these mice also differed in the severity of withdrawal seizures following consumption of an ethanol-containing liquid diet but did not differ in ethanol intake. In contrast to ethanol withdrawal seizures, the lines displayed similar sensitivity to electrical- or pentylenetetrazole-induced seizures. These results suggest that the lines differ in the development of physical dependence on ethanol rather than seizure sensitivity per se. Because decreased synaptic membrane fluidity has been associated with ethanol dependence, we used fluorescence polarization of diphenylhexatriene and trimethylammonium-diphenylhexatriene to evaluate membrane fluidity in WSP and WSR mice fed lab chow, an ethanol-containing liquid diet, or an isocaloric sucrose-containing liquid diet. Fluidity of brain synaptic membranes was identical for WSP and WSR mice fed lab chow. The control liquid diet did not alter membrane fluidity, and the ethanol diet decreased fluidity equally for WSP and WSR mice. Thus, the genetic difference in development of ethanol dependence found in these lines was not reflected in the physical properties of brain membranes.
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PMID:Relationship of membrane physical properties to alcohol dependence in mice selected for genetic differences in alcohol withdrawal. 654 19

A major goal of pharmacogenetic research on alcoholism remains the identification of some "marker" that could predict the liability of a particular individual for a genetic susceptibility to develop alcoholism. The present paper presents evidence that the severity of withdrawal from physical dependence on ethanol varies widely among inbred strains of mice, and that withdrawal severity is negatively genetically correlated with initial sensitivity and magnitude of tolerance to ethanol hypothermia. These correlations are supported by differences in hypothermic response between replicate lines of mice genetically selected for susceptibility and resistance to ethanol withdrawal seizures. The genetic relationships reported suggest that the effects of ethanol on thermoregulation in mice may offer a predictive marker for susceptibility to ethanol physical dependence.
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PMID:Genetic correlations with ethanol withdrawal severity. 668 10


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