Psychopharmacology

, Volume 197, Issue 4, pp 591–600

Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats

Authors

    • Merck, Sharp and Dohme, Terlings Park, CM21 2QR
  • W. F. Sheppard
    • Merck, Sharp and Dohme, Terlings Park, CM21 2QR
    • Merck and Co. West Point
  • S. M. Staveley
    • Merck, Sharp and Dohme, Terlings Park, CM21 2QR
    • Discovery Biology Pfizer Ltd.
  • B. Sohal
    • Merck, Sharp and Dohme, Terlings Park, CM21 2QR
    • Novartis Horsham Research Centre
  • F. D. Tattersall
    • Merck, Sharp and Dohme, Terlings Park, CM21 2QR
    • Discovery Biology Pfizer Ltd.
  • P. H. Hutson
    • Merck, Sharp and Dohme, Terlings Park, CM21 2QR
    • Merck and Co. West Point
Original Investigation

DOI: 10.1007/s00213-008-1077-z

Cite this article as:
McDonald, L.M., Sheppard, W.F., Staveley, S.M. et al. Psychopharmacology (2008) 197: 591. doi:10.1007/s00213-008-1077-z

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

Copyright information

© Springer-Verlag 2008