Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats
| Autor: | L.M. McDonald, S. M. Staveley, Peter H. Hutson, F. D. Tattersall, W. F. Sheppard, B. Sohal |
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| Rok vydání: | 2006 |
| Předmět: |
Agonist
Male medicine.medical_specialty Zolpidem Baclofen GABA Plasma Membrane Transport Proteins Tiagabine Cyclohexanecarboxylic Acids medicine.drug_class GABA Agents Pyridines Nipecotic Acids Administration Oral Thiophenes Pharmacology Bicuculline Piperazines Discrimination Learning GABA Antagonists Benzodiazepines Internal medicine medicine Animals Hypnotics and Sedatives Amines GABA Agonists gamma-Aminobutyric Acid Dose-Response Relationship Drug GABAA receptor Chemistry Brain Isoxazoles Rats Endocrinology nervous system Generalization Stimulus Indiplon GABAergic Anticonvulsants Gabapentin Azabicyclo Compounds Gaboxadol Injections Intraperitoneal medicine.drug |
| Zdroj: | Psychopharmacology. 197(4) |
| ISSN: | 0033-3158 |
| Popis: | Rationale Tiagabine is an anticonvulsant drug which may also have sleep-enhancing properties. It acts by inhibiting reuptake at the gamma-aminobutyric acid (GABA) transporter (GAT-1). Objectives The aim of the study was to determine whether tiagabine acted asa discriminativestimulusand,ifso, whether other GABAergic compounds would generalise to it. Materials and methods Rats were trained to discriminate tiagabine (30 mg/kg p.o.) from vehicle, and generalisation to drugs that modulate GABA was assessed. Results Gaboxadol (5–20 mg/kg p.o.), a selective extrasynaptic GABAA agonist, generalised to tiagabine, although the extent of the generalisation was inconclusive. Indiplon (1 mg/kg p.o.), a benzodiazepine-like hypnotic, also partially generalised to tiagabine, although zolpidem and S-zopiclone did not. Baclofen, a GABAB receptor agonist, and gabapentin, which increases synaptic GABA, did not generalise to tiagabine. (+)-Bicuculline (3 mg/kg i.p.), a GABAA receptor antagonist, blocked the tiagabine cue, but the less brainpenetrant salt form, bicuculline methochloride, had no effect. Conclusions These data suggest that tiagabine generates a discriminative stimulus in rats, and provides a central GABA-mediated cue, but is distinct from the other GABAergic compounds tested. |
| Databáze: | OpenAIRE |
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