C. Belzung et al., Anxiolytic-like effects of meprobamate: Interactions with an opiate antagonist in swiss and BALB/c mice, PHARM BIO B, 65(3), 2000, pp. 465-474
Naloxone has previously been shown to block the effects of benzodiazepines
in the Swiss but not in the BALB/c strain. We have also reported that nalox
one potentiates subeffective doses of benzodiazepines in Swiss mice. In the
present studies we first determined whether naloxone could block anxiolyti
c-like effects of meprobamate in Swiss and BALB/c mice. Then we evaluated i
f subeffective doses of meprobamate could be potentiated in Swiss as well a
s in BALB/c mice. The elevated plus-maze test and the light/dark choice pro
cedure were used. The lowest dose of meprobamate with anxiolytic-like effec
ts was 60 mg/kg in the BALB/c mice. This dose was effective in both the plu
s-maze and in the light/dark choice procedure. In Swiss mice the same dose
was effective in the plus-maze, whereas 120 mg/kg was required in the light
/dark choice procedure. When an effective dose of meprobamate was combined
with naloxone, 10 mg/kg, no blockade of anxiolytic-like effects was obtaine
d in any strain in any procedure. To the contrary, when a subeffective dose
of meprobamate was combined with naloxone, 10 mg/kg, an anxiolytic-like ef
fect was obtained in both strains in both procedures. The present series of
experiment shows that the ability of naloxone to block anxiolytic-like dru
g effects do not apply to meprobamate. However, the naloxone-induced potent
iation of subeffective doses previously observed after treatment with benzo
diazepines or buspirone was present also after treatment with meprobamate.
Moreover, although blockade of anxiolytic-like drug effects with naloxone h
as not been observed in BALB/c mice, potentiation was as evident in that st
rain as in the Swiss. This suggests that the mechanisms behind naloxone's b
lockade of anxiolytic-like effects are independent from those behind its po
tentiation of such effects. (C) 2000 Elsevier Science Inc.