Low but not high doses of buspirone reduce the anxiogenic effects of diazepam withdrawal |
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Authors: | Sandra E. File Nick Andrews |
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Affiliation: | (1) Psychopharmacology Research Unit, UMDS Division of Pharmacology, London University, Guy's Hospital, SE1 9RT London, UK |
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Abstract: | After 21 days of treatment with diazepam (2 mg/kg/day IP) rats were tested 24 h after the last injection in the social interaction and elevated plus-maze tests of anxiety. Compared with control-treated rats, they showed significant decreases in social interaction, in the % numbers of entries onto open arms of the plus-maze and in the % of time spent on the open arms, indicating an anxiogenic response on withdrawal from diazepam. Buspirone (200 µg/kg SC) significantly increased social interaction in diazepam withdrawn rats and in the plus-maze also this dose significantly reversed the anxiogenic effects of diazepam withdrawal. Buspirone (400 µg/kg SC) was without effect in the plus-maze, but buspirone (800 µg/kg SC) significantly decreased the % of time spent on open arms in control-treated rats, indicating an anxiogenic effect. In the social interaction test buspirone (800 µg/kg SC) was without significant effect. The contrasting effects of the 200 and 800 µg/kg doses are discussed in terms of the pre- and post-synaptic actions of buspirone. The findings are consistent with earlier proposals that the increased anxiety during benzodiazepine withdrawal is at least partly caused by an increased release of hippocampal 5-HT. |
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Keywords: | Benzodiazepine Withdrawal Anxiety 5-HT1A receptors |
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