Alcohol dependence and withdrawal: a genetic animal model. 1990

J C Crabbe, and C M Merrill, and D Kim, and J K Belknap
Research Service, Department of Veterans Affairs Medical Center, Portland, Oregon 97201.

Using the techniques of selective breeding, mouse lines have been developed that express severe (Withdrawal Seizure Prone: WSP) or mild (Withdrawal Seizure Resistant: WSR) handling induced convulsions after cessation of chronic ethanol exposure. These lines differ at least ten-fold in severity of withdrawal after identical ethanol treatment. One feature of the genetic model is that other traits which distinguish these lines are presumably influenced by those genes determining ethanol withdrawal severity. WSP and WSR mice do not differ markedly in the metabolism of ethanol. In addition to handling induced convulsions, they also differ in other withdrawal signs: for example, WSP mice show more pronounced tremor. WSP and WSR mice do not differ in sensitivity to ethanol's hypothermic, anesthetic, or locomotor stimulant effects, nor in the magnitude of tolerance development to these responses. This suggests that sensitivity, tolerance and dependence are distinct genetic entities. WSP mice also display more severe withdrawal from diazepam, phenobarbital, and nitrous oxide than WSR mice, suggesting that some genes generally predispose mice to withdrawal from depressants. WSP mice display withdrawal handling induced convulsions after a single dose of ethanol, pentobarbital, or diazepam. The effective dose for producing drug seizures is not markedly different between WSP and WSR mice for a number of compounds with varied mechanisms of action. However, WSP mice are more sensitive than WSR mice to the effects of acute doses of convulsants to elevate handling induced convulsions. WSP mice have more binding sites in hippocampus for the N-methyl-D-aspartate antagonist MK 801. Binding of this ligand is increased during ethanol dependence in both mouse lines.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004198 Disease Susceptibility A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. Diathesis,Susceptibility, Disease,Diatheses,Disease Susceptibilities,Susceptibilities, Disease
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000437 Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4) Alcohol Abuse,Alcoholic Intoxication, Chronic,Ethanol Abuse,Alcohol Addiction,Alcohol Dependence,Alcohol Use Disorder,Abuse, Alcohol,Abuse, Ethanol,Addiction, Alcohol,Alcohol Use Disorders,Chronic Alcoholic Intoxication,Dependence, Alcohol,Intoxication, Chronic Alcoholic,Use Disorders, Alcohol
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
D012640 Seizures Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder." Absence Seizure,Absence Seizures,Atonic Absence Seizure,Atonic Seizure,Clonic Seizure,Complex Partial Seizure,Convulsion,Convulsions,Convulsive Seizure,Convulsive Seizures,Epileptic Seizure,Epileptic Seizures,Generalized Absence Seizure,Generalized Tonic-Clonic Seizures,Jacksonian Seizure,Myoclonic Seizure,Non-Epileptic Seizure,Nonepileptic Seizure,Partial Seizure,Seizure,Seizures, Convulsive,Seizures, Focal,Seizures, Generalized,Seizures, Motor,Seizures, Sensory,Tonic Clonic Seizure,Tonic Seizure,Tonic-Clonic Seizure,Atonic Absence Seizures,Atonic Seizures,Clonic Seizures,Complex Partial Seizures,Convulsion, Non-Epileptic,Generalized Absence Seizures,Myoclonic Seizures,Non-Epileptic Seizures,Nonepileptic Seizures,Partial Seizures,Petit Mal Convulsion,Seizures, Auditory,Seizures, Clonic,Seizures, Epileptic,Seizures, Gustatory,Seizures, Olfactory,Seizures, Somatosensory,Seizures, Tonic,Seizures, Tonic-Clonic,Seizures, Vertiginous,Seizures, Vestibular,Seizures, Visual,Single Seizure,Tonic Seizures,Tonic-Clonic Seizures,Absence Seizure, Atonic,Absence Seizure, Generalized,Absence Seizures, Atonic,Absence Seizures, Generalized,Auditory Seizure,Auditory Seizures,Clonic Seizure, Tonic,Clonic Seizures, Tonic,Convulsion, Non Epileptic,Convulsion, Petit Mal,Convulsions, Non-Epileptic,Focal Seizure,Focal Seizures,Generalized Seizure,Generalized Seizures,Generalized Tonic Clonic Seizures,Generalized Tonic-Clonic Seizure,Gustatory Seizure,Gustatory Seizures,Motor Seizure,Motor Seizures,Non Epileptic Seizure,Non Epileptic Seizures,Non-Epileptic Convulsion,Non-Epileptic Convulsions,Olfactory Seizure,Olfactory Seizures,Partial Seizure, Complex,Partial Seizures, Complex,Seizure, Absence,Seizure, Atonic,Seizure, Atonic Absence,Seizure, Auditory,Seizure, Clonic,Seizure, Complex Partial,Seizure, Convulsive,Seizure, Epileptic,Seizure, Focal,Seizure, Generalized,Seizure, Generalized Absence,Seizure, Generalized Tonic-Clonic,Seizure, Gustatory,Seizure, Jacksonian,Seizure, Motor,Seizure, Myoclonic,Seizure, Non-Epileptic,Seizure, Nonepileptic,Seizure, Olfactory,Seizure, Partial,Seizure, Sensory,Seizure, Single,Seizure, Somatosensory,Seizure, Tonic,Seizure, Tonic Clonic,Seizure, Tonic-Clonic,Seizure, Vertiginous,Seizure, Vestibular,Seizure, Visual,Seizures, Generalized Tonic-Clonic,Seizures, Nonepileptic,Sensory Seizure,Sensory Seizures,Single Seizures,Somatosensory Seizure,Somatosensory Seizures,Tonic Clonic Seizures,Tonic-Clonic Seizure, Generalized,Tonic-Clonic Seizures, Generalized,Vertiginous Seizure,Vertiginous Seizures,Vestibular Seizure,Vestibular Seizures,Visual Seizure,Visual Seizures
D013375 Substance Withdrawal Syndrome Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug. Drug Withdrawal Symptoms,Withdrawal Symptoms,Drug Withdrawal Symptom,Substance Withdrawal Syndromes,Symptom, Drug Withdrawal,Symptom, Withdrawal,Symptoms, Drug Withdrawal,Symptoms, Withdrawal,Syndrome, Substance Withdrawal,Syndromes, Substance Withdrawal,Withdrawal Symptom,Withdrawal Symptom, Drug,Withdrawal Symptoms, Drug,Withdrawal Syndrome, Substance,Withdrawal Syndromes, Substance
D015032 Zinc A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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