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.
KeywordsTiagabine GABA Drug discrimination Rat Gaboxadol Indiplon Baclofen Gabapentin Bicuculline Bicuculline methochloride
Many thanks to Professor Ian Stolerman for his excellent advice on designing these studies and to Dr. Keith Wafford for his invaluable help in discussing the data. Also, special thanks to Andrew Jack for excellent statistical advice.
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