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


OBJECTIVE
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.


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.
McDonald
L M
LM
Merck, Sharp and Dohme, Terlings Park, CM21 2QR, Harlow, Essex, UK. LouiseMcDonald1@gmail.com
Sheppard
W F
WF
Staveley
S M
SM
Sohal
B
B
Tattersall
F D
FD
Hutson
P H
PH
D000284:Administration, Oral; D000588:Amines / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology; D001418:Baclofen / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018682:GABA Agents / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins / Q000187:drug effects; D000077206:Gabapentin; D005795:Generalization, Stimulus / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013876:Thiophenes / Q000494:pharmacology; D000078308:Tiagabine; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D000927:Anticonvulsants; D053961:Azabicyclo Compounds; D003509:Cyclohexanecarboxylic Acids; D018682:GABA Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D006993:Hypnotics and Sedatives; D007555:Isoxazoles; D009557:Nipecotic Acids; D010879:Piperazines; D011725:Pyridines; D013876:Thiophenes; C515050:zopiclone; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000077334:Zolpidem; C469870:indiplon; D001418:Baclofen; C006749:bicuculline methochloride; C015542:gaboxadol; D001640:Bicuculline; D000078308:Tiagabine