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Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats.
Psychopharmacology (Berl). 2008 May; 197(4):591-600.P

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.

Authors+Show Affiliations

Merck, Sharp and Dohme, Terlings Park, CM21 2QR, Harlow, Essex, UK. LouiseMcDonald1@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

18264695

Citation

McDonald, L M., et al. "Discriminative Stimulus Effects of Tiagabine and Related GABAergic Drugs in Rats." Psychopharmacology, vol. 197, no. 4, 2008, pp. 591-600.
McDonald LM, Sheppard WF, Staveley SM, et al. Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats. Psychopharmacology (Berl). 2008;197(4):591-600.
McDonald, L. M., Sheppard, W. F., Staveley, S. M., Sohal, B., Tattersall, F. D., & Hutson, P. H. (2008). Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats. Psychopharmacology, 197(4), 591-600. https://doi.org/10.1007/s00213-008-1077-z
McDonald LM, et al. Discriminative Stimulus Effects of Tiagabine and Related GABAergic Drugs in Rats. Psychopharmacology (Berl). 2008;197(4):591-600. PubMed PMID: 18264695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats. AU - McDonald,L M, AU - Sheppard,W F, AU - Staveley,S M, AU - Sohal,B, AU - Tattersall,F D, AU - Hutson,P H, Y1 - 2008/02/09/ PY - 2006/12/19/received PY - 2008/01/10/accepted PY - 2008/2/12/pubmed PY - 2008/8/30/medline PY - 2008/2/12/entrez SP - 591 EP - 600 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 197 IS - 4 N2 - 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/18264695/Discriminative_stimulus_effects_of_tiagabine_and_related_GABAergic_drugs_in_rats_ L2 - https://dx.doi.org/10.1007/s00213-008-1077-z DB - PRIME DP - Unbound Medicine ER -