Protracted ethanol withdrawal in rats: Tolerance to the anxiolytic effects of diazepam and pentobarbital but not phenobarbital
- Texas Coll. of Osteopathic Medicine, Fort Worth (United States)
Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats were trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats exhibited signs and symptoms of withdrawal which returned to baseline within 3 days. During the protracted withdrawal period, the authors then redetermined the blockade of the PTZ-IDS. Significant tolerance was observed to the effectiveness of diazepam and pentobarbital, but not to phenobarbital. Since diazepam and pentobarbital produce significantly more enhancement of GABAergic activity than does phenobarbital, these data further suggest alteration of brain GABAergic systems during protracted withdrawal from ethanol.
- OSTI ID:
- 6053945
- Report Number(s):
- CONF-9104107-; CODEN: FAJOE
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 4:3; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BARBITURATES
BIOCHEMICAL REACTION KINETICS
ETHANOL
TOXICITY
BRAIN
INGESTION
RATS
SYMPATHOLYTICS
TOLERANCE
ALCOHOLS
ANESTHETICS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BODY
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
HYPNOTICS AND SEDATIVES
INTAKE
KINETICS
MAMMALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PYRIMIDINES
REACTION KINETICS
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology