Attenuation of benzodiazepine withdrawal anxiety in the rat by serotonin antagonists

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• 作者：Begg ; Denovan P. ; Hallam ; Karen T. ; Norman ; Trevor R.
• 关键词：Benzodiazepine withdrawal ; 5-HT₂ antagonists ; Anxiety ; Elevated plus maze ; Social interaction test ; Diazepam
• 刊名：Behavioural Brain Research
• 出版年：2005
• 期刊代码：3_01664328
• 类别：neu
• 出版时间：June 20, 2005
• 卷：161
• 期：2
• 页码：286-290
• 文件大小：105 K

摘要

Administration of benzodiazepines is known to be associated with tolerance and a withdrawal syndrome on abrupt cessation. The aetiology of the withdrawal syndrome is not known but a role for the serotonin (5HT) system is suspected. The aim of the current study was to investigate the usefulness of 5-HT₂ antagonists in the treatment of benzodiazepine withdrawal syndrome in the rat. Male Wistar rats were treated with either diazepam (4 mg/kg) or vehicle for 14 days, then abruptly withdrawn for 24 h. Animals were tested in the social interaction paradigm and elevated plus maze. Some diazepam-withdrawn rats were pre-treated with 5HT₂ antagonists 60 min before behavioural testing. Acute withdrawal from benzodiazepines significantly reduced social interaction between pairs compared to vehicle or diazepam-treated animals. Similarly, for the elevated plus maze withdrawn animals made fewer entries and spent less time on the open arms than did vehicle or diazepam-treated animals. Single doses of 5-HT₂ antagonists, mianserin (5 mg/kg) and ritanserin (1 mg/kg), effectively ameliorated withdrawal anxiety in the rat, returning behavioural function in the social interaction test and elevated plus maze to levels comparable to vehicle-treated animals.