No abstract

The mammalian central nervous system contains noradrenaline (Vogt, 1954) and 5-hydroxytryptamine (Amin, Crawford & Gaddum, 1954), but study of the possible central functions of these amines poses particular problems. One of these is that parenterally injected amines may elicit a central effect by a peripheral action. For example, behavioural and electrocortical arousal is produced not only by amphetamine, which readily penetrates to the brain, but also by catechol amines, which do not readily cross the blood-brain barrier. Although the central nervous system is clearly involved in both instances, the similarity in effect does not indicate whether the primary action of the amine is central, peripheral or both. Indeed, if the blood-brain barrier is circumvented and an apparently potent excitant, such as adrenaline, is given intracisternally (Leimdorfer, 1950) or intraventricularly (Feldberg & Sherwood, 1954) (Goldstein & Muftoz, 1961) and, on the other, to an action mediated through cardiovascular a-receptors (Capon, 1960). The behavioural effects of catechol amines are thought to be determined predominantly through central nervous a-receptors (Wurtman, Frank, Morse & Dews, 1959;Dews, 1962). Munioz & Goldstein (1961) considered that the excitant effects of amphetamine were also mediated through central nervous a-receptors. Vane (1960), however, showed that amphetamine acted on tryptamine receptors in the smooth muscle of the rat stomach and suggested that a similar action might take place in the brain. Additional emphasis in this direction was provided by the observation that monoamine oxidase inhibitors, which potentiate central excitants, lead to different effects on the excretion of the enzyme substrates in the urine, since the concentration of tryptamine showed much the greatest increase compared with that of 5-hydroxytryptamine and the metanephrines (Dewhurst, 1961). Any examination therefore of the actions of sympathomimetic amines on the central nervous system should include tests of the effects of tryptamines.

This paper reports a case which is noteworthy for two unrelated reasons, one genetic and the other therapeutic. The genetic interest lies in the rare instance of an identical twin with obsessive compulsive neurosis whose twin brother had a similar illness. The therapeutic interest focuses on clinical changes which occurred during unsuccessful treatment by desensitization and by aversion relief. These changes aid our understanding of compulsive behaviour and the difficulties in its treatment. At one stage in treatment independence was noted between anxiety and compulsions which suggested that compulsive behaviour need not always be maintained by its anxiety-reducing properties. The case history will first be described and discussed from the genetic point of view. The second part of this paper will focus on the unrelated aspect of treatment.

The effects of the a-methyl derivatives of noradrenaline, phenethylamine and tryptamine on the central nervous system of the chicken have been described (Dewhurst & Marley, 1965a). In the present experiments a larger series of amines and of their amino acid precursors has been tested on the central nervous system and on blood pressure. In addition, factors potentiating activity such as monoamine oxidase inhibition or diminishing activity such as tachyphylaxis or pharmacological antagonism have been studied.Preliminary accounts of this work have been presented (Dewhurst & Marley, 1964, and communication to the British Pharmacological Society, January, 1964). METHODSThe methods used for implanting electrodes and cannulae and for measuring cheeping and electrocortical and electromyographic activity were the same as those described previously (Dewhurst & Marley, 1965a,b). In addition to 1-to 28-day-old chickens, fowls up to 1 year old were used.To record blood pressure in the conscious unrestrained chicken a polyethylene cannula sealed with a nylon spigot and containing heparin-saline (100 mg/ml.) was tied into the upper part of a carotid artery; the tubing was brought through the scalp incision and fixed to the skull and wound into the strand of electrodes and the venous cannula. In the experiments in which electrocortical activity and blood pressure were recorded, the cortical electrodes were implanted on the left cerebral hemisphere and the blood pressure cannula was tied into the right carotid artery. At the time of the experiment, the spigot was removed and the arterial catheter was connected via saline-filled polyethylene tubing to a tap unit and screening micrometer transducer. The signals were amplified and displayed on a D.E. potentiometric recorder (Cambridge Instruments).Other blood pressure experiments were made with spinal chickens. These were prepared with halothane and oxygen anaesthesia given by endotracheal tube. After destroying the brain through an occipital craniotomy, the animal was artificially ventilated with a Palmer Miniature Ideal respiration pump. Excess air was allowed to escape through an adjustable leak in the circuit and round the endotracheal cannula. Blood pressure was recorded with a transducer connected to a cannula in the carotid or the ischiadic artery.Chromatography was carried out with the apparatus and techniques devised by Smith (1960). Amines were applied as the salts (detailed below) dissolved in 50% methanol in water to give an amine concentration of 10 pmoles/ml. Spots (1 id.) were applied with a Hamilton syringe. The major component of the developing solvent was oleyl alcohol (B.D.H.) which had been washed successively with equal volumes of N-sodium hydroxide, de-ionized water, N-hydrochloric acid, further water until washings were neutral and then shaken with an equal volume of 0.1 N-ammonifm acetate buffer, pH 7.4, for 20 min. The two