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 beta 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 delta 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.
Different kinetics of tolerance to behavioral and electroencephalographic effects of chlordiazepoxide in the rat / M. Sala, M.P. Leone, P. Lampugnani, D. Braida, E. Gori. - In: EUROPEAN JOURNAL OF PHARMACOLOGY. - ISSN 0014-2999. - 273:1/2(1995), pp. 35-45.
|Titolo:||Different kinetics of tolerance to behavioral and electroencephalographic effects of chlordiazepoxide in the rat|
SALA, MARIAELVINA (Primo)
BRAIDA, DANIELA (Penultimo)
|Parole Chiave:||(Rat); Behavior; Chronic chlordiazepoxide; Dependence; EEG (electroencephalographic); Tolerance|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||1995|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/0014-2999(94)00665-T|
|Appare nelle tipologie:||01 - Articolo su periodico|