On the effects of diazepam, hyoscine and oxotremorine on acetylcholine release from the cerebral cortex.

The amount of acetylcholine (ACh) released in perplex cylinders filled with 0.5 ml eserinized Ringer solution and placed on the exposed rat cerebral cortex was determined every 10 min. For the purpose bioassay on leech dorsal muscle was used. ACh was calculated in pmoles/cm2 min-1. It was found that diazepam decreased by 30 per cent, hyoscine increased by 36 per cent and oxotremorine also decreased by 24.5 per cent the ACh output from the cerebral cortex. Hyoscine counteracted to a considerable extent the diazepam-induced inhibition of ACh output, but oxotremorine did not potentiate the inhibitory effect of diazepam on ACh output, in some cases it even prevented it. It could be assumed that the effects of hyoscine and oxotremorine result to a considerable extent from their action on presynaptic autoinhibitory muscarinic receptors. However, it is also possible for the effects of oxotremorine to be important influences on the cortical cholinergic mechanisms, mediated by adrenergic structures. The results obtained suggest a definite role of the cerebral cholinergic system in the mechanism of action of the benzodiazepine derivative diazepam.