The effect of leptazol and strychnine on the acetylcholine release from the cat brain.

Abstract

In anaesthetized cats perfusion of the cerebral ventricles with an anticholinesterase provides a simple method for studying the effect of centrally active drugs on the release of acetylcholine from structures bordering the ventricular cavities. On perfusion with neostigmine from lateral ventricle to aqueduct, acetylcholine appears in the effluent and this acetylcholine is mainly derived from the caudate nucleus (Bhattacharya & Feldberg, 1958c;Beleslin, Carmichael & Feldberg, 1964); this output is reduced by morphine and chloralose, two central depressant drugs (Beleslin & Polak, 1965).The present experiments show that intravenous injections of two convulsant drugs, leptazol and strychnine, have the opposite effect, and cause an increased output of acetylcholine in the aqueductal effluent.Electrical stimulation of the caudate nucleus also leads to an increased output in the effluent. Further it is shown that the action of leptazol and strychnine is not confined to the caudate nucleus, but that these convulsant drugs have a similar action on the acetylcholine release from the cerebral cortex.Our findings are in agreement with two previous observations. First, Mitchell (1963) found in sheep that an intravenous injection of leptazol increases the release of acetylcholine from the cerebral cortex. Secondly, Mitchell & Szerb (1962) using the push-pull cannula technique of Gaddum (1961), found an increased release of acetylcholine from the caudate nucleus, on electrical stimulation of this nucleus in cats. METHODSCats of 20-2-5 kg body weight were anaesthetized with chloralose, 45-65 mg/kg, given intravenously through a cannula inserted in the femoral vein under ethyl chloride anaesthesia, and tracheotomy was performed. The femoral artery was cannulated for recording of the arterial blood pressure, using a Cambridge transducer and a Leeds and Northrop * Wellcome Research Fellow.t NATO Science Fellow.

The effect of central stimulant drugs on acetylcholine release from rat cerebral cortex

“…These results are in agreement with those of Celesia & Jasper (1966), who applied strychnine topically to the brain of the cat and obtained only a 50% increase in ACh release from the cortex even when generalized strychninization with widespread discharges had occurred. The results differ from those of Beleslin et al (1965), however, who obtained with intravenous strychnine a large increase in the ACh release from the parietal cortex of the cat. Their different result may be due to the use of the intravenous route of administration of strychnine in contrast to intraperitoneal injection or topical application, but this would not explain why the ACh release was so much smaller in these two conditions in spite of the relatively strong effect on the electrical activity of the brain.…”

“…The increased ACh release produced by leptazol confirms findings of Mitchell (1963), Beleslin, Polak & Sproull (1965) and Celesia & Jasper (1966). The large increase in ACh release caused by leptazol was accompanied by a correspondingly large increase in the electrical activity of the brain.…”

Effects of nicotine on electrocortical activity and acetylcholine release from the cat cerebral cortex

“…Convulsant drugs such as leptazol have been shown to increase ACh output in cats (Mitchell, 1963;Beleslin et al, 1965;Celesia & Jasper, 1966), and rats (Hemsworth & Neal, 1968). That nicotine caused the opposite effect may result from differences in site of action because nicotine induces seizure discharge by an action on the hippocampus (Floris et al, 1964) whereas leptazol exerts its effects on other cortical and subcortical structures.…”

Chemical structure and biological activity of the diazepines.

“…It may also explain the anticonvulsant effect of diazepines against pentetrazol. This drug probably has no GABA-or glycine-antagonistic properties which could explain its convulsant activity, but has stimulatory effects on cholinergic neuronal activity, emanating from a massive release of acetylcholine (Beleslin et al, 1965;Hemsworth & Neal, 1968).…”