S. Korkmaz et al., COMPARATIVE EFFECTS OF DIAZEPAM, FLUMAZENIL AND BUSPIRONE ON BENZODIAZEPINE WITHDRAWAL ANXIETY, Neuroscience research communications, 14(3), 1994, pp. 125-132
Although it is known that tolerance develops to the anxiolytic effect
of diazepam and a spontaneous withdrawal anxiogenesis appears followin
g cessation of chronic drug administration, not only the mechanism by
how tolerance develops but the extent of effects and the mechanism of
action of drugs on withdrawal anxiety are not yet clearly defined. In
the present study, a dose dependent anxiolytic effect of diazepam was
shown via Elevated Plus Maze. While buspirone produced a significant a
nxiolysis flumazenil had no effect on the parameters studied, in naive
rats. Not only tolerance development to the anxiolytic effect of diaz
epam but a significant withdrawal anxiety was shown in chronically dia
zepam treated rats. Diazepam was found to produce a significant anxiol
ysis against withdrawal anxiety, but buspirone, flumazenil and buspiro
ne-flumazenil combination were all found to reverse the withdrawal anx
iety limited to the control base line level. Diazepam and flumazenil c
ombination was also found to produce a significant anxiolysis but not
as potent as diazepam.