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Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats.

Mcdonald, Lisa and Sheppard, W F and Staveley, S M and Sohal, Bindi and 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
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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
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Date Deposited: 14 Dec 2009 13:51
Last Modified: 14 Dec 2009 13:51
URI: https://oak.novartis.com/id/eprint/889

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