On the involvement of GABA in the analgesia produced by baclofen, muscimol and morphine

In the mouse hot-plate test (50°C), muscimol produced analgesia which was blocked by bicuculline but not by picrotoxin. Analgesia produced by baclofen was dose-dependent and stereoselective, but was not blocked by bicuculline, picrotoxin or naloxone. Morphine-induced analgesia was not altered by bicuculline. The inhibitors of GABA-transaminase, amino-oxyacetic acid, γ-acetylenic GABA and γ-vinyl GABA, produced analgesia which was much more prolonged than that observed with muscimol, baclofen or morphine. The analgesic action of these agents was not significantly altered by bicuculline. At a higher plate temperature (55°C), GABA-transaminase inhibitors produced minimal analgesia but significantly enhanced the analgesic action of baclofen. γ- Vinyl GABA markedly increased both the peak effect and the duration of analgesia but γ-acetylenic GABA and amino-oxyacetic acid caused smaller increases. In the mouse hot-plate test, bicuculline-sensitive GABA receptors appear to mediate the analgesic action of muscimol. Analgesia produced by baclofen, morphine and inhibitors of GABA-transaminase may involve another class of GABA receptors which are insensitive to bicuculline.