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 either the benzodiazepine diazepam (1.5 mg/kg) or the imidazopyridine zolpidem (0.05 mg/kg), the latter two acting differentially on GABA(A) receptor subtypes. 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 behavior. Treatment with the low dose of tiagabine alone induced no specific behavioral effects, whereas the high dose had an anxiolytic-like potential. Furthermore, diazepam but not zolpidem displayed anxiolytic-like effects. Combination of each benzodiazepine receptor agonist with tiagabine at the low dose decreased explorative activity. Diazepam plus the high dose of tiagabine increased the activity in the open-field test. Zolpidem together with 18.5 mg/kg tiagabine had an angiogenic-like effect compared to pure tiagabine treatment. These results provide evidence for a pharmacodynamic interaction between the GABA-uptake inhibitor tiagabine and diazepam or zolpidem. The interaction might be relevant in the clinic when combining the anticonvulsant tiagabine and a benzodiazepine receptor agonist.
Schmitt
U
U
Department of Psychiatry, University of Mainz, Germany.
Lüddens
H
H
Hiemke
C
C
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D050485:GABA Plasma Membrane Transport Proteins; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D026901:Membrane Transport Proteins; D009043:Motor Activity / Q000187:drug effects*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology*; D027361:Organic Anion Transporters; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D000078308:Tiagabine; D000077334:Zolpidem
D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D006993:Hypnotics and Sedatives; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D011725:Pyridines; D011963:Receptors, GABA-A; D000077334:Zolpidem; D000078308:Tiagabine