Doubtful Value of Bicuculline as a Specific Antagonist of GABA

Abstract

IN view of the recent report that bicuculline^1–3 antagonizes the action of γ-aminobutyric acid (GABA) at various sites in the central nervous system⁴ we have systematically tested this alkaloid, applied by microiontophoresis to neurones in the cerebral cortex of four cats under ‘Dial’ anaesthesia. Two samples of bicuculline were used: the first was obtained from Pierce Chemicals; it was prepared either as a 0.1 M solution in dioxane, or by dissolving at a concentration of 0.05–0.1 M in dilute HCl (final pH 3). The second sample (bicuculline hydrochloride) was kindly given to us by Dr R. Manske (University of Waterloo): this was prepared as in the experiments of Curtis et al.⁴ at a concentration of 10 mM in 165 mM NaCl (pH 4). One barrel of the multi-barrelled glass micropipettes was filled with these solutions 2–3 days before the experiments. The 0.1 M solutions did not readily pass iontophoretic currents > 30–50 nA (see ref. 4), but very large currents (≫100 nA) could be passed through the 10 mM solutions for several tens of minutes.