TY - JOUR
T1 - Different kinetics of tolerance to behavioral and electroencephalographic effects of chlordiazepoxide in the rat
AU - Sala, Mariaelvina
AU - Leone, Maria Primula
AU - Lampugnani, Paola
AU - Braida, Daniela
AU - Gori, Enzo
PY - 1995/1/24
Y1 - 1995/1/24
N2 - 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.
AB - 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.
KW - (Rat)
KW - Behavior
KW - Chronic chlordiazepoxide
KW - Dependence
KW - EEG (electroencephalographic)
KW - Tolerance
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U2 - 10.1016/0014-2999(94)00665-T
DO - 10.1016/0014-2999(94)00665-T
M3 - Article
C2 - 7737317
AN - SCOPUS:0028955643
VL - 273
SP - 35
EP - 45
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-2
ER -