Different kinetics of tolerance to behavioral and electroencephalographic effects of chlordiazepoxide in the rat

The daily oral administration of chlordiazepoxide (40 mg/kg) over 9 weeks in rats elicited full tolerance to muscle relaxant effects within 7 weeks, as revealed by twice weekly evaluations of abdominal tone myorelaxation and decreased grip strength. No full tolerance was achieved, however, during th...

Full description

Saved in:
Bibliographic Details
Published in:European journal of pharmacology 1995-01, Vol.273 (1), p.35-45
Main Authors: Sala, Mariaelvina, Leone, Maria Primula, Lampugnani, Paola, Braida, Daniela, Gori, Enzo
Format: Article
Language:English
Subjects:
Animals
Anticonvulsants - pharmacology
Behavior
Behavior, Animal - drug effects
Biological and medical sciences
Body Weight - drug effects
Chlordiazepoxide - pharmacology
Chronic chlordiazepoxide
Dependence
Drug Tolerance
EEG (electroencephalographic)
Electroencephalography - drug effects
Kinetics
Male
Medical sciences
Muscle Relaxation - drug effects
Neuropharmacology
Pharmacology. Drug treatments
Psycholeptics: tranquillizer, neuroleptic
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rat
Rats
Rats, Wistar
Substance Withdrawal Syndrome - physiopathology
Tolerance
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The daily oral administration of chlordiazepoxide (40 mg/kg) over 9 weeks in rats elicited full tolerance to muscle relaxant effects within 7 weeks, as revealed by twice weekly evaluations of abdominal tone myorelaxation and decreased grip strength. No full tolerance was achieved, however, during the 9 weeks of treatment in terms of ataxia. Electroencephalographic (EEG) studies showed that this tolerance to the behavioural effects was accompanied by a progressive decrease in mean power spectra, associated with a progressive decrease in the β band, but in this case, full tolerance was reached within 4 weeks. Once weekly evaluations of the ability of chlordiazepoxide to protect the animals against pentylenetetrazole seizures revealed a similar pattern. Treatment with flumazenil (50 mg/kg p.o.) 24 h after the last chlordiazepoxide administration induced a clear withdrawal syndrome associated with EEG changes which consisted of an increase in total power spectra associated with an increase in the δ band (in comparison with chlordiazepoxide-dependent rats not given the antagonist). These findings suggest that the different kinetics of the tolerance to anticonvulsant and EEG effects in comparison to myorelaxant effects can be attributed to a different involvement of benzodiazepine receptor subtypes.
ISSN:0014-2999
1879-0712
DOI:10.1016/0014-2999(94)00665-T