Anxiolytic-like effects of meprobamate. Interactions with an opiate antagonist in Swiss and BALB/c mice.
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 naloxone potentiates subeffective doses of benzodiazepines in Swiss mice. In the present studies we first determined whether naloxone could block anxiolytic-like effects of meprobamate in Swiss and BALB/c mice. Then we evaluated if subeffective doses of meprobamate could be potentiated in Swiss as well as in BALB/c mice. The elevated plus-maze test and the light/dark choice procedure were used. The lowest dose of meprobamate with anxiolytic-like effects was 60 mg/kg in the BALB/c mice. This dose was effective in both the plus-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 obtained 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 effect was obtained in both strains in both procedures. The present series of experiment shows that the ability of naloxone to block anxiolytic-like drug effects do not apply to meprobamate. However, the naloxone-induced potentiation of subeffective doses previously observed after treatment with benzodiazepines or buspirone was present also after treatment with meprobamate. Moreover, although blockade of anxiolytic-like drug effects with naloxone has not been observed in BALB/c mice, potentiation was as evident in that strain as in the Swiss. This suggests that the mechanisms behind naloxone's blockade of anxiolytic-like effects are independent from those behind its potentiation of such effects.
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Laboratoire d'Ethologie et Pharmacologie du Comportement, Faculté des Sciences, Université de Tours, Tours, France.
Le Guisquet
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Agmo
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D008297:Male; D008620:Meprobamate / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects
D014151:Anti-Anxiety Agents; D009292:Narcotic Antagonists; D011963:Receptors, GABA-A; D009270:Naloxone; D008620:Meprobamate