Behavioral effects of GABA(A) receptor stimulation and GABA-transporter inhibition

The present analysis addressed behavioral changes after treatment with 4.5 mg/kg or 18.5 mg/kg of the GABA-uptake inhibitor tiagabine combined with ei ther the benzodiazepine diazepam (1.5 mg/kg) or the imidazopyridine zolpide m (0.05 mg/kg), the latter two acting differentially on GABA(A) receptor su btypes. The study included 97 male PVG/OIaHsd rats. A standard open field, an enriched open field, and an elevated plus-maze was used to study rat beh avior. Treatment with the low dose of tiagabine alone induced no specific b ehavioral effects, whereas the high dose had an anxiolytic-like potential. Furthermore, diazepam but not zolpidem displayed anxiolytic-like effects. C ombination of each benzodiazepine receptor agonist with tiagabine at the lo w dose decreased explorative activity. Diazepam plus the high dose of tiaga bine increased the activity in the open-field test. Zolpidem together with 18.5 mg/kg tiagabine had an angiogenic-like effect compared to pure tiagabi ne treatment. These results provide evidence for a pharmacodynamic interact ion between the GABA-uptake inhibitor tiagabine and diazepam or zolpidem. T he interaction might be relevant in the clinic when combining the anticonvu lsant tiagabine and a benzodiazepine receptor agonist. (C) 2000 Elsevier Sc ience Inc.