Abstract
Potentially life-threatening seizures can occur following withdrawal from benzodiazepines, ethanol, or barbiturates. In animals, withdrawal severity has been shown to be partially genetically determined for each drug class. Susceptibility to these drugs is partially determined by common genetic factors, but the evidence is conflicting. We tested the hypothesis that acute benzodiazepine withdrawal convulsions are influenced by at least some genes that also affect withdrawal from ethanol and pentobarbital. Results in inbred mouse strains demonstrate that strain susceptibility is genetically correlated with susceptibility to ethanol and pentobarbital. The proportion of variance accounted for by genetic factors common to diazepam and ethanol was estimated at 69%. Results contrast with previous data obtained in mice that were serially tested for withdrawal severity from ethanol, pentobarbital, and then diazepam, because serial testing of mice significantly affected the previous results for some strains. Diazepam withdrawal severity was also genetically correlated with pentobarbital withdrawal. Together, these results suggest that some genes influence severity of withdrawal from several types of depressant drugs. Copyright (C) 1999 Elsevier Science Inc.
Original language | English (US) |
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Pages (from-to) | 473-479 |
Number of pages | 7 |
Journal | Pharmacology Biochemistry and Behavior |
Volume | 63 |
Issue number | 3 |
DOIs | |
State | Published - Jul 1999 |
Externally published | Yes |
Keywords
- Benzodiazepines
- Diazepam
- Ethanol
- Flumazenil
- Genetic correlation
- Genetic determinants
- Handling-induced convulsions
- Inbred strains
- Mouse
- Pentobarbital
- Pharmacogenetics
- Withdrawal
ASJC Scopus subject areas
- Biochemistry
- Toxicology
- Pharmacology
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience