Irreversibility of kindled alcohol-withdrawal behaviour in rats. 1998

J Ulrichsen, and S Haugbøl, and C F Brandt, and P Allerup, and R Hemmingsen
Department of Psychiatry--6214, Rigshospitalet, Copenhagen, Denmark.

In order to investigate whether alcohol-withdrawal kindling is an irreversible process, male Wistar rats were exposed to 12 episodes, each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. Spontaneous withdrawal seizures were found in 15% of the animals during episodes 10-12. After an alcohol-free period of 26 days, the animals were subjected to three more episodes of alcohol dependence (i.e. episodes 13-15) in which 12% of the animals developed spontaneous withdrawal seizures. Based on several statistical tests, we concluded that there was no true difference between the seizure activity in episodes 10-12 and episodes 13-15, indicating that alcohol-withdrawal kindling is a long-lasting and perhaps irreversible process. In a second experiment, an alcohol-withdrawal kindled group was first exposed to seven episodes of alcohol dependence. A diazepam group went through the same alcohol regimen, but each withdrawal reaction was blocked by diazepam treatment. Finally, a single episode group was included which was fed isocalorically with the kindled animals. After an alcohol-free period of 11 days, all three groups were subjected to 4 days of severe alcohol intoxication. During the subsequent withdrawal reaction seizures were observed in 22-26% of the animals with no significant differences across the groups. These results call for a modification of the kindling hypothesis of alcohol withdrawal and suggest that kindling-induced alterations may be overlooked if convulsive behaviour is tested during a relatively strong withdrawal reaction.

UI MeSH Term Description Entries
D007696 Kindling, Neurologic The repeated weak excitation of brain structures, that progressively increases sensitivity to the same stimulation. Over time, this can lower the threshold required to trigger seizures. Kindlings, Neurologic,Neurologic Kindling,Neurologic Kindlings
D008297 Male Males
D003975 Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004569 Electroencephalography Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. EEG,Electroencephalogram,Electroencephalograms
D000430 Alcohol Withdrawal Delirium An acute organic mental disorder induced by cessation or reduction in chronic alcohol consumption. Clinical characteristics include CONFUSION; DELUSIONS; vivid HALLUCINATIONS; TREMOR; agitation; insomnia; and signs of autonomic hyperactivity (e.g., elevated blood pressure and heart rate, dilated pupils, and diaphoresis). This condition may occasionally be fatal. It was formerly called delirium tremens. (From Adams et al., Principles of Neurology, 6th ed, p1175) Alcohol Withdrawal Hallucinosis,Autonomic Hyperactivity, Alcohol Withdrawal Associated,Delirium Tremens,Alcohol Withdrawal Associated Autonomic Hyperactivity,Alcohol Withdrawal-Induced Delirium Tremens,Delirium Tremens, Alcohol Withdrawal Induced,Alcohol Withdrawal Induced Delirium Tremens,Delirium, Alcohol Withdrawal,Hallucinosis, Alcohol Withdrawal
D000435 Alcoholic Intoxication An acute brain syndrome which results from the excessive ingestion of ETHANOL or ALCOHOLIC BEVERAGES. Drunkenness,Intoxication, Alcoholic,Drunkennesses
D000679 Amygdala Almond-shaped group of basal nuclei anterior to the INFERIOR HORN OF THE LATERAL VENTRICLE of the TEMPORAL LOBE. The amygdala is part of the limbic system. Amygdaloid Body,Amygdaloid Nuclear Complex,Amygdaloid Nucleus,Archistriatum,Corpus Amygdaloideum,Intercalated Amygdaloid Nuclei,Massa Intercalata,Nucleus Amygdalae,Amygdalae, Nucleus,Amygdaloid Bodies,Amygdaloid Nuclear Complices,Amygdaloid Nuclei, Intercalated,Amygdaloid Nucleus, Intercalated,Amygdaloideum, Corpus,Amygdaloideums, Corpus,Archistriatums,Complex, Amygdaloid Nuclear,Complices, Amygdaloid Nuclear,Corpus Amygdaloideums,Intercalata, Massa,Intercalatas, Massa,Intercalated Amygdaloid Nucleus,Massa Intercalatas,Nuclear Complex, Amygdaloid,Nuclear Complices, Amygdaloid,Nuclei, Intercalated Amygdaloid,Nucleus, Amygdaloid,Nucleus, Intercalated Amygdaloid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014151 Anti-Anxiety Agents Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here. Anti-Anxiety Agent,Anti-Anxiety Drug,Anxiolytic,Anxiolytic Agent,Anxiolytic Agents,Tranquilizing Agents, Minor,Anti-Anxiety Drugs,Anti-Anxiety Effect,Anti-Anxiety Effects,Antianxiety Effect,Antianxiety Effects,Anxiolytic Effect,Anxiolytic Effects,Anxiolytics,Tranquillizing Agents, Minor,Agent, Anti-Anxiety,Agent, Anxiolytic,Agents, Anti-Anxiety,Agents, Anxiolytic,Agents, Minor Tranquilizing,Agents, Minor Tranquillizing,Anti Anxiety Agent,Anti Anxiety Agents,Anti Anxiety Drug,Anti Anxiety Drugs,Anti Anxiety Effect,Anti Anxiety Effects,Drug, Anti-Anxiety,Drugs, Anti-Anxiety,Effect, Anti-Anxiety,Effect, Antianxiety,Effect, Anxiolytic,Effects, Anti-Anxiety,Effects, Antianxiety,Effects, Anxiolytic,Minor Tranquilizing Agents,Minor Tranquillizing Agents

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