Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats.
Tools
Tools
Mcdonald, Lisa, Sheppard, W F, Staveley, S M, Sohal, Bindi, Tattersall, F D and Hutson, P H (2008) Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats. Psychopharmacology, 197 (4). pp. 591-600. ISSN 0033-3158
Abstract
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 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. RESULTS: 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. 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.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Additional Information: | author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used |
| Keywords: | Tiagabine; GABA; Drug discrimination; Rat; Gaboxadol; Indiplon; Baclofen; Gabapentin; Bicuculline; Bicuculline methochloride |
| Related URLs: | |
| Date Deposited: | 14 Dec 2009 13:51 |
| Last Modified: | 14 Dec 2009 13:51 |
| URI: | https://oak.novartis.com/id/eprint/889 |