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

Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats

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



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.


Tiagabine 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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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • L. M. McDonald
    • 1
    Email author
  • 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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