Anxiolytic-like effects of 5-HT(1A) agonists in drug-naive and in benzodiazepine-experienced rats.
The efficacy of two 5-HT(1A) receptor agonists in drug-naive and benzodiazepine-experienced rats was compared in two animal tests of anxiety, the social interaction and elevated plus-maze tests. Benzodiazepine-experienced rats were tested 48h after the last of 28 daily injections of diazepam (2mg/kg/day), a time at which there was no anxiogenic withdrawal response. S20499 (0.04, 0.2 and 1mg/kg) ((+)-8(4-[N-(5-methoxychroman-3yl)N-propylamine]butyl)-8-azaspirol[4,5]decane-7,9-dione) and buspirone (0.2mg/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 0.2mg/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-HT(1A) receptor agonists in animal tests of anxiety as a result of prior diazepam treatment.
Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London SE1 9RT, UK.
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