Anxiolytic-like effects of acute and chronic GABA transporter inhibition in rats.
Acute GABA transporter inhibition can induce anxiolytic-like behaviors. The present analysis addressed whether chronic treatment (23 days via drinking water) with a GABA transporter inhibitor affects rat behavior similar to acute treatment and interferes with additional benzodiazepine-receptor agonistic treatment. Seventy-one rats divided into seven groups were acutely treated with either vehicle, diazepam (2 mg/kg), zolpidem (0.05 mg/kg), tiagabine (19 mg/kg) or chronically with tiagabine with or without acute diazepam or zolpidem. Animals were behaviorally characterized in an elevated plus-maze. None of the treatments induced changes in the activity of the animals. Acute and chronic treatment with tiagabine induced anxiolytic-like effects, similar to acute doses of diazepam. Acute diazepam did not enhance chronic tiagabine effects, whereas acute zolpidem attenuated the anxiolytic-like effects of chronic tiagabine. It is concluded that anxiolytic effects of acute GABA-uptake inhibition by tiagabine persist under chronic treatment and are sensitive to concomitant use of benzodiazepine receptor ligands.
Department of Psychiatry, University of Mainz, Mainz, Federal Republic of Germany.
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Schmitt
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Lüddens
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Hiemke
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D050485:GABA Plasma Membrane Transport Proteins; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D027361:Organic Anion Transporters; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D000078308:Tiagabine; D013997:Time Factors; D000077334:Zolpidem
D014151:Anti-Anxiety Agents; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D011725:Pyridines; D000077334:Zolpidem; D003975:Diazepam; D000078308:Tiagabine