Effects of some benzodiazepines on the acetylcholine release in the anterior horn of the lateral cerebral ventricle of the cat.

Studies were made of the effects of the benzodiazepines clonazepam (Cz), flunitrazepam (Fz) and Diazepam (Dz) on the spontaneous release of acetylcholine (ACh) in the anterior horn of the lateral cerebral ventricle of cats superficially anaesthetized with urethane. The amount of released ACh was determined in 15-min samples by a bioassay on a segment from isolated guinea-pig ileum. It was found that benzodiazepines applied i.p. in doses of: 5 mg/kg (Dz), 10 mg/kg (Cz) and 0.5 mg/kg (Fz) decreased the ACh release in the effluent flowing out through the cannulated aqueduct. If the released ACh in the sample taken immediately before the administration of benzodiazepine was considered to be 100 per cent its amount in the samples after injection of benzodiazepine changed as follows (in per cent): for Dz - 34.2, 70.2, 65.7, 40; for Cz - 46.3, 33.1, 26, 50.6; and for Fz - 46.1, 46.1, 28.2, 39.4. It is assumed that the benzodiazepine-induced reduced release of ACh from the caudate nucleus--a main structure participating in the building up of the anterior horn of the lateral cerebral ventricle--is a manifestation of inhibition of ACh turnover which might be due to inhibition of the activity of the serotoninergic neurons in the raphe nuclei. The decreased ACh release might also be due to inhibition by benzodiazepines of the Ca2+-dependent release of ACh.