Dikshit (1935) injected acetylcholine in doses of 0.1-1.0 jg into the lateral ventricles of conscious cats and observed a condition resembling sleep that lasted for 2-3 hr. Feldberg & Sherwood (1954a) observed drowsiness or stupor in cats after similar injections of acetylcholine in doses of 1 tig or less. However, with doses of 10-20 ,ug they observed that the cats emitted a high-pitched cry and retched, and later went into a condition resembling akinetic seizure. When large doses of 1 mg acetylcholine were injected into the cerebral ventricles of cats general convulsions were produced, followed later by stupor (Feldberg & Sherwood, 1954b). No studies are available, however, on the effects of intracarotid injections of acetylcholine in conscious animals, which would expose the brain to a higher coneentration of the drug than the rest of the body. Bradley (1960) injected small amounts of acetylcholine (5 ng) into the carotid artery of the cat (enciphale isol6 preparation) and observed activation of the electroencephalogram.In the present experiments with conscious dogs, the effects of intracarotid injections, as well as infusions of acetylcholine, were studied. In addition to acetylcholine, its antagonists, atropine, d-tubocurarine and hexamethonium, and the anticholinesterase drugs neostigmine and physostigmine were administered into the carotid artery, and the effects were observed. METHODSThe experiments were performed on 31 dogs of either sex weighing 6.8-14.9 kg. Operative procedures Carotid loopsThe carotid arteries were placed in skin loops under aseptic conditions in five dogs under pentobarbitone anaesthesia. A procedure similar to that described by Himwich, Costa, Canham & Goldstein (1960) was followed with some modifications. The common carotid artery was dissected distally to about 2 cm above the origin of the thyroid artery (which was ligated and severed) and proximally to about 3 cm above the root of the neck. The freed artery was included in a skin pedicle. Care was taken not to close too tightly the sites of entry and exit of the artery in the skin pedicle, so that the artery was not constricted by fibrous tissue at the time of healing. In one dog the external carotid artery was ligated before it divided into branches.

Stern & Gautier (1921) detected atropine in the cerebrospinal fluid of the dog and of the rabbit, after its intravenous or intracarotid injection. The present experiments were undertaken to see if in the cat also atropine passes from the blood stream into the cerebrospinal fluid, and if so, to determine the rate of its output in the effluents obtained on perfusion of various parts of the cerebral ventricles and subarachnoid space.Our experiments with cats show that atropine, during its intravenous infusion, appears in the cerebrospinal fluid, and further it was found in the effluents from both the perfused cerebral ventricles and the perfused subarachnoid space. There was no significant difference between the output from the cerebral ventricles and that from the subarachnoid space. METHODSCats weighing 1.5 to 4 kg were anaesthetized with chloralose, 70 mg/kg, injected intravenously under ethyl chloride and-ether anaesthesia. The trachea was cannulated. For the atropine infusion a cannula was inserted in the right femoral vein. The atropine sulphate in 0.9% saline was infused at 0.2 ml./min with a continuous slow injector at rates of 1, 10 or 25 pLg/kg/min. Blood samples were obtained from the left femoral artery, which was dissected free and clamped; an opening was made in the artery for the insertion at intervals of 1 hr of a polythene tube, through which the samples were collected into tubes containing heparin, and then immediately centrifuged and the plasma separated. The plasma was kept at room temperature (25 to 300 C) if assayed on the same day, or in the refrigerator (at 4' C) for assay on the next day.Collection of cerebrospinal fluid. A cisternal cannula similar to one described by Bhawe (1958) was inserted into the cisterna magna. The cannula consisted of a 20 S.W.G. hypodermic needle with the butt removed and a small length of polythene tube attached. The free end of the polythene tube was closed with a small glass stillete. Cerebrospinal fluid samples were collected every hr by removing the glass stillete and allowing 0.5 to I ml. of cerebrospinal fluid to flow into a test tube. The stillete was then replaced.