Effects of buspirone, diazepam, and zolpidem on open field behavior, and brain [H-3]muscimol binding after buspirone pretreatment

The effects of 5-HT1A receptor agonist buspirone, a nonselective (diazepam) , and a selective (zolpidem) GABA(A) receptor agonist were compared in the open field test of neophobia. Unhabituated rats were pretreated with the dr ugs once, prior to a first exposure to the open field, and their behavior w as recorded both during this test and during a second trial 24 h later. It has been hypothesized that the decrease in exploratory activity observed du ring the second test session may be considered an adaptive reaction to the first day aversive experience (neophobia). If so. a selective modulation of 5-HT and GABA systems activity during the test could bring about significa nt changes in animal behavior on the retest. Buspirone at the lowest dose o f 0.3 mg/kg revealed anxiolytic-like properties on the first day, whereas t he action of diazepam and zolpidem was modulated by the dose-related sedati ve effect. At the dose of 2.4 mg/kg buspirone elicited delayed in time anxi olytic-like action, i.e., produced the antithigmotactic effect during the r etrial 24 h later. Diazepam and zolpidem failed to exhibit similar profile of action. Autoradiography of [H-3]muscimol binding after pretreatment of r ats with buspirone showed a significant increase in the selective radioliga nd binding within the frontal cortex and a similar, near-significant tenden cy in the dentate gyrus of the hippocampus. The behavioral data validate bu spirone as important drug for the treatment of anxiety disorders, devoid of disruptive influence on motor and cognitive processes. The open field test , as modified by us, appeared sensitive in distinguishing the behavioral pr ofiles of action of different anxiolytic compounds, including 5-HT1A recept or agonist. The present results support the assumption that reduced turnove r of 5-HT due to stimulation of 5-HT1A autoreceptors, may bring about chang es in GABA(A) receptor system activity, in some brain structures, leading t o the anxiolytic effect. (C) 2000 Elsevier Science Inc.