Bhawe (1958) has shown that when histamine is injected into the lateral cerebral ventricle of an anaesthetized cat acid gastric secretion occurs. This secretion was attributed to passage of histamine into the blood stream and it was assumed that the histamine had passed from the ventricles into the subarachnoid space and then into the endocranial venous sinuses. The present experiments show that histamine also passes into the blood stream from the cerebral ventricles without entering the subarachnoid space. In addition, it was found that histamine perfused through the cerebral ventricles entered the brain tissue surrounding the ventricular cavities and that this uptake ofhistamine showed differences dependent on the structures of the ventricular wall.
METHODSThe experiments were carried out in cats anaesthetized by intraperitoneal injection of pentobarbitone sodium 35 mg/kg; additional pentobarbitone was injected when it became necessary in the course of the experiment. The trachea was cannulated. Histamine was usually perfused through the lateral and third ventricles. The fourth ventricle was not included in the perfusion since, in order to prevent the perfusion fluid from entering into the subarachnoid space, the effluent was collected from a cannula inserted into the aqueduct, as described by Bhattacharya & Feldberg (1956). The effluent was assayed for histamine after its volume had been measured. The absorption of histamine into the blood stream was shown by estimating the acid gastric secretion.Perfuaion of cerebral ventricle8. The fluid used for perfusion was that introduced by Merlis (1940) and later used by Leusen (1949). Its composition, which is approximately that of normal cerebrospinal fluid, is as follows (g/l.): NaCl 8-1; KCI 0-25; CaCl2 0-14; MgCl2 0*11; NaHCO3 1P76; NaH2P04 0 07; CO(NH2)2 0-13; and glucose 0-61. This solution will be referred to as artificial cerebrospinal fluid (artificial c.s.f.). A Collison cannula was implanted into the left lateral ventricle as described by Feldberg & Sherwood (1953). The perfusion was maintained by a continuous slow injector (C. F. Palmer, Ltd.) at a rate of 0-1 ml./min. In order to insert the outflow cannula into the aqueduct the muscle layers covering the atlantooccipital membrane and the lower part of the occipital bone were dissected away, and the
On the isolated rat uterus, lysergic acid diethylamide had an oxytocic action in a concentration of 2 x 10-8; in smaller concentrations (I0-9 to 10-10), which had no stimulating effect of their own, it potentiated acetylcholine-induced contractions. This potentiating effect was made the basis for assaying minute amounts of lysergic acid diethylamide. The method was used to assay this substance in plasma of cats during its intravenous infusion at a rate of 10 tug./min./kg.During these infusions 0.4 to 2 ng./min. of lysergic acid diethylamide passed into the cerebral ventricles perfused with a salt solution of a composition resembling that of cerebrospinal fluid.The present experiments show that minute doses of lysergic acid diethylamide augment acetylcholine-induced contractions of the isolated rat uterus, and this effect can provide the basis for a simple, sensitive method of assay of lysergic acid diethylamide. This method was used in experiments on cats during which lysergic acid diethylamide was infused intravenously, to measure the plasma concentration of the drug and to detect its appearance in the fluid with which the cerebral ventricles and the subarachnoidal space of the brain were perfused.Apart from determinations of labelled lysergic acid diethylamide, only two methods have been used previously for the assay of this drug. Lanz, Cerletti and Rothlin (1955) used the inhibition which lysergic acid diethylamide exerts on the contractions of the rat uterus induced by 5-hydroxytryptamine, and they were able to assay amounts of 1 to 2 ng./ml. 24 hr. before they were killed, and one uterine horn was suspended in a bath containing 5 ml. of the solution which was used by Gaddum, Peart and Vogt (1949) for the assay of adrenaline on the rat uterus. This solution contained NaCl 9, KCl 0.42, CaC12 0.06, NaHCO3 0.50 and dextrose 0.5 g. /1. of distilled water. The bath fluid was bubbled with oxygen and was maintained at 30'. The quantities of acetylcholine refer to the chloride.
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