Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats
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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).
The aim of the study was to determine whether tiagabine acted as a discriminative stimulus and, if so, 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.
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 brain-penetrant salt form, bicuculline methochloride, had no effect.
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.
- Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats
Volume 197, Issue 4 , pp 591-600
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- Drug discrimination
- Bicuculline methochloride
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- Author Affiliations
- 1. Merck, Sharp and Dohme, Terlings Park, CM21 2QR, Harlow, Essex, UK
- 2. Merck and Co. West Point, Pennsylvania, USA
- 3. Discovery Biology Pfizer Ltd., Ramsgate Road, Sandwich, CT13 9NJ, UK
- 4. Novartis Horsham Research Centre, Wimblehurst Road, Horsham, RH12 5AB, UK