title: Attenuation of benzodiazepine withdrawal anxiety in the rat by serotonin antagonists.
abstract: 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 Male Wistar rats were treated with either diazepam (4 mg/kg) or vehicle for 14 days, then abruptly withdrawn for 24h. 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 Some diazepam-withdrawn rats were pre-treated with 5HT2 antagonists 60 min before behavioural testing.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 Similarly, for the elevated plus maze withdrawn animals made fewer entries and spent less time on the open arms than did vehicle or diazepam-treated animals.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 (5mg/kg) and ritanserin (1mg/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.
authors.affiliation: La Trobe University School of Psychological Science, Australia.
authors.forename: Denovan P
authors.initials: DP
authors.lastname: Begg
authors.forename: Karen T
authors.initials: KT
authors.lastname: Hallam
authors.forename: Trevor R
authors.initials: TR
authors.lastname: Norman
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects*; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal; D003975:Diazepam / Q000009:adverse effects*; D004195:Disease Models, Animal; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008803:Mianserin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016713:Ritanserin / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000209:etiology*; D013997:Time Factors
chemical_list: D014151:Anti-Anxiety Agents; D012702:Serotonin Antagonists; D016713:Ritanserin; D008803:Mianserin; D003975:Diazepam