Role of cholinergic mechanisms in the mechanism of action of bicuculline

Abstract

The hypothesis of a possible role of cholinergic structures in the mechanism of the action of bicuculline was tested by screening and electrophysiological methods. Neither muscarinic (M-) nor nicotinic (N-) cholinolytics (benactyzine, atropine, aprophen,^* and pediphen^†) abolished convulsions produced in mice by bicuculline. Meanwhile substances inducing the accumulation of γ-aminobutyric acid (GABA) in the brain, such as aminohydroxyacetic acid (AHAA) and depakine, had a well marked protective action against bicuculline convulsions. The electrophysiological experiments also showed that the M-cholinolytic benactyzine does not abolish the effects of bicuculline. Bicuculline was shown to reduce the depression of the test response in the recovery cycle of the primary response of the rat sensomotor cortex when intervals between stimuli measured 40–125 msec, whereas benactyzine reduced the late facilitation of the test response when intervals between stimuli measured 150–300 msec. No interaction could be found between benactyzine and bicuculline by this test. It was concluded from these results that the effects of bicuculline are produced by blockade of postsynaptic GABA receptors and are not connected with the activity of cholinergic structures.