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Persistent reversal of tolerance to anticonvulsant effects and GABAergic subsensitivity by a single exposure to benzodiazepine antagonist during chronic benzodiazepine administration

SF Gonsalves and DW Gallager

Yale University School of Medicine, Department of Psychiatry, New Haven, Connecticut.

The persistence of benzodiazepine antagonists in reversing neuronal and behavioral tolerance during chronic diazepam exposure was examined in rodents by investigating the time course for antagonist-induced alterations in iontophoretic sensitivity to gamma-aminobutyric acid on dorsal raphe neurons and the re-emergence of anticonvulsant efficacy to bicuculline-induced seizures. In these studies, exposure to Ro15-1788 resulted in the persistent reversal of GABAergic subsensitivity and restoration of anticonvulsant actions of diazepam despite the continued presence of diazepam in the rats. Reversal of tolerance appears to persist for up to 7 days after a single exposure to benzodiazepine antagonists.

Volume 244, Issue 1, pp. 79-83, 01/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.