Psychopharmacology

, Volume 197, Issue 4, pp 591–600 | Cite as

Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats

  • L. M. McDonald
  • W. F. Sheppard
  • S. M. Staveley
  • B. Sohal
  • F. D. Tattersall
  • P. H. Hutson
Original Investigation

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 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.

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.

Keywords

Tiagabine GABA Drug discrimination Rat Gaboxadol Indiplon Baclofen Gabapentin Bicuculline Bicuculline methochloride 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • L. M. McDonald
    • 1
  • W. F. Sheppard
    • 1
    • 2
  • S. M. Staveley
    • 1
    • 3
  • B. Sohal
    • 1
    • 4
  • F. D. Tattersall
    • 1
    • 3
  • P. H. Hutson
    • 1
    • 2
  1. 1.Merck, Sharp and Dohme, Terlings Park, CM21 2QRHarlow, EssexUK
  2. 2.Merck and Co. West PointPennsylvaniaUSA
  3. 3.Discovery Biology Pfizer Ltd.SandwichUK
  4. 4.Novartis Horsham Research CentreHorshamUK

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