Effects of GABA-transporter (GAT) inhibitors on rat behaviour in open-field and elevated plus-maze.
The behavioural consequences of inhibition of gamma-aminobutyric acid (GABA) uptake were studied. Two GABA uptake inhibitors, tiagabine and SKF 89976-A, were administered to rats, and behaviour was analysed 30 min later in a standard open field, an enriched open field, and an elevated plus-maze. Eight groups of animals received either saline (0.9%), tiagabine, or SKF 89976-A. At a dose of 18.5 mg/kg, tiagabine, an established antiseizure drug, impaired motor coordination, enhanced exploratory activity and reduced anxiety related behaviour. SKF 89976-A exhibited minimal effects over the dose range tested. These results indicate that inhibition of GABA uptake might be a pharmacological strategy to treat not only epilepsy, but also anxiety disorders.
Schmitt
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U
Department of Psychiatry, University of Mainz, Germany.
Hiemke
C
C
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004777:Environment; D005106:Exploratory Behavior / Q000187:drug effects; D018682:GABA Agents / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D026901:Membrane Transport Proteins; D009043:Motor Activity / Q000187:drug effects; D009557:Nipecotic Acids / Q000494:pharmacology; D027361:Organic Anion Transporters; D051381:Rats; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D002352:Carrier Proteins; D018682:GABA Agents; D018755:GABA Agonists; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; D000078308:Tiagabine