Gaboxadol, a selective extrasynaptic GABAA agonist, does not generalise to other sleep-enhancing drugs: A rat drug discrimination study

Abstract Gaboxadol is a selective extrasynaptic GABA A receptor agonist (SEGA) which enhances slow-wave sleep, and may act principally at extrasynaptic GABA A α4βδ receptors. Drug discrimination is a very useful approach for exploring in vivo pharmacological similarities and differences between compounds and was therefore used to compare gaboxadol and zolpidem, an established hypnotic drug, against zopiclone, S-zopiclone, indiplon and tiagabine, all of which have been reported to enhance sleep. Gaboxadol generalised to itself, but not to zolpidem, zopiclone, S-zopiclone, R-zopiclone, indiplon or tiagabine. By contrast, zolpidem generalised to itself, zopiclone, S-zopiclone and indiplon, but not to R-zopiclone (the inactive enantiomer of zopiclone), gaboxadol or tiagabine. This suggests that zolpidem, zopiclone, S-zopiclone and indiplon share a discriminative stimulus, which may be mediated by their efficacy at GABA A α1βγ receptors. Gaboxadol and tiagabine each have a different discriminative stimulus from all the other drugs tested.