Experiments on the site of action of tubocurarine when applied via the cerebral ventricles

Abstract

In the present experiments an attempt was made to locate the site where tubocurarine acts to produce the convulsive effects and the accompanying changes in electrical activity of the brain on injection into the lateral cerebral ventricle. Two different approaches were made. By recording the electrical activity from two points on either side of the mid line, it could be demonstrated that the activity produced by the unilateral injection occurred with similar latencies on both sides. This excludes structures lining the lateral ventricles as the sites at which the activity originated. In the course of these experiments it was found that records obtained from the cellular layer of Ammon's horn during the action of tubocurarine showed a characteristic pattern different from the patterns found in any other region so far examined.In the second approach the tubocurarine was perfused through a cannula ending in the lateral ventricle and the effluent was collected from various points between the third ventricle and the cisterna. In these experiments the muscular effects were recorded on a myograph and changes in excitability tested by the response of the quadriceps muscle to tapping its tendon. METHODSThe experiments were performed on cats under chloralose anaesthesia (60 mg/kg intravenously).In experiments in which records were taken of the electrical activity of the brain and in which evoked responses to peripheral nerve stimulation (peroneal nerve) were recorded before and after an intraventricular injection of tubocurarine, the methods used were those previously described (Feldberg, Malcolm & Smith, 1957), and tubocurarine was injected intravenously. In those experiments in which tubocurarine was perfused through a cannula in the lateral ventricle and the effluent was collected from the cisterna or the aqueduct, the methods were essentially those described by Feldberg & Bhattacharya (1958), but the perfusion fluid used was not always Locke's solution but often an 'artificial cerebrospinal fluid' introduced by Merlis (1940) and later used by Leusen (1949). Its composition was as follows (g/l.): NaCl 8-10, KCI 0-25, CaCI2 014, MgCl2 0-11, NaHCO3 1-76, NaH2PO4 0 07, (NH2)2CO 0-13, glucose 0*61. No difference was observed in the effects of tubocurarine when Locke's solution or artificial c.s.f. was used for perfusion. The rate of * Present address: Department of Physiology, Marischal College, Aberdeen.

The strychnine‐like action of curare and related compounds on the somatosensory evoked response of the rat cortex

“…Both substances induce spontaneous spike discharges and lead to similar modifications in topically evoked responses. Subsequently the convulsant action of intraventricularly administered D-tubocurarine was studied by Feldberg and colleagues (Feldberg, Malcolm, & Sherwood, 1956: Feldberg & Malcolm, 1959Feldberg, 1963). The increase in the surface negative component of responses evoked in the somatosensory cortex by peripheral stimulation was shown by Cairnie & Malcolm (1960) to follow a direct local action of D-tubocurarine on the cerebral cortex.…”

The site of origin of the seizure discharge produced by tubocurarine acting from the cerebral ventricles

“…However, he gave no indication of the site where tubocurarine acts when evoking this discharge. More recently profound changes in the electrical activity of the brain have been recorded with micro-electrodes from various cortical and subcortical regions after intraventricular injections of tubocurarine (Feldberg, Malcolm & Sherwood, 1956;Feldberg, Malcolm & IDarian Smith, 1957;Feldberg & Malcolm, 1959), but attempts to locate the site of this action of tubocurarine failed. Thus Feldberg & Malcolm (1959) were unable 'to decide the pertinent question of where the tubocurarine acts when, on intraventricular injection, it produces the profound changes in the electrical activity of the brain which we presume to be associated with the convulsive activity'.…”

The site of origin of the tremor produced by tubocurarine acting from the cerebral ventricles

“…The finding that tremor is produced by an action of tubocurarine on the hypothalamus is at variance with the statement by Feldberg & Malcolm (1959) that the most sensitive regions where tubocurarine produces muscular effects including tremor are those surrounding the aqueduct. In some of their experiments they found that the aqueduct was excluded 550 TUBOCURARINE TREMOR from perfusion because the tip of the outflowing cannula was lying at the opening into the third ventricle.…”