Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats

Abstract

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. 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 GABA A 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 GABA B receptor agonist, and gabapentin, which increases synaptic GABA, did not generalise to tiagabine. (+)-Bicuculline (3 mg/kg i.p.), a GABA A 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.