Anxiolytic-like effects of 5-HT1A agonists in drugnaive and in benzodiazepine-experienced rats

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The efficacy of two S-HT1A receptor agonists in drug-naive and benzodiazepine-experienced rats was compared in two animal vests of anxiety, the social interaction and elevated plus-maze tests. Benzodiazepine-experienced rats were tested 48 h after the last of 28 daily injections of diazepam (2mg/kg/day), a time at which there was no anxiogenic withdrawal response. S 20499 (0.04, 0.2 and 1 mg/kg) ((+)-8(4–[N-(5-methoxychroman-3yl)N-propylamine]butyl)-8-azaspiro[4,5]decane-7,9-dione) and buspirone (0.2 mg/kg) significantly increased social investigation, indicating anxiolytic-like actions, and there was no significant modification in these effects as a result of the previous diazepam treatment. Both drugs also significantly reduced aggressive behaviours in both drug-naive and diazepam-experienced rats. An anxiolytic-like action in the elevated plus-maze was also indicated for S 20499 (0.04 and 0.2 mg/kg) by an increase in the percentage of time spent on the open arms; this effect was not significantly changed by prior diazepam experience. Buspirone (0.2mg/kg) had no significant effects on the plus-maze. The results provide no evidence for reduced efficacy of 5-HT1A receptor agonists in animal tests of anxiety as a result of prior diazepam treatment.

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