Low but not high doses of buspirone reduce the anxiogenic effects of diazepam withdrawal.
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 Buspirone (200 micrograms/kg SC) significantly increased social interaction in diazepam withdrawn rats and in the plus-maze also this dose significantly reversed the anxiogenic effects of diazepam withdrawal.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 micrograms/kg SC) was without effect in the plus-maze, but buspirone (800 micrograms/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 micrograms/kg SC) was without significant effect. The contrasting effects of the 200 and 800 micrograms/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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Psychopharmacology Research Unit, UMDS Division of Pharmacology, London University, Guy's Hospital, UK.
Andrews
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D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D002065:Buspirone / Q000008:administration & dosage*; D003975:Diazepam / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D011897:Random Allocation; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D003975:Diazepam; D002065:Buspirone