In rats, a series of anticonvulsant compounds have been shown to cause a significant elevation of brain 5-hydroxytryptamine (5-HT) levels in comparison with control values. This increase in 5-HIT only occurred in brain tissue and was not observed in spleen, upper small intestine or blood. Elevation of brain levels of 5-HT by iproniazid (Marsilid) or 5-hydroxytryptophan failed to give protection against the convulsant or lethal action of lept-zol (75 mg./kg.).The effect of phenytoin (diphenylhydantoin, Dilantin) in preventing the response of the pituitary-adrenal system to various standard procedures, known to cause a discharge of the adrenocorticotrophic hormone (ACTH) and a resultant fall in adrenal ascorbic acid, has been studied both for a direct action of the drug upon the adrenal gland itself and a possible alteration in some central mechanism (Bonnycastle andBradley, 1956, 1957). As it appeared fairly clear that, initially at least, the interference with the response is central in origin since the adrenal cortex remains normal in its responsiveness to exogenous trophic hormone, it was of interest to examine the levels of one or other of the suggested transmitting substances in the brain. In a preliminary report (Bonnycastle, Paasonen and Giarman, 1956) the 5-hydroxytryptamine (5-HT) content of the brains of rats treated with phenytoin was shown to be elevated approximately twofold over that of untreated control animals. The present paper deals with the brain levels of 5-HT in rats treated with other anti-epileptic drugs in use. Unlike phenytoin, none of these substances has any inhibitory effect upon the pituitary-adrenal system. METHODSMale rats of the Sprague-Dawley strain weighing 100 to 300 g. were used in these experiments. The compounds listed in Table I were examined. While the dosage varied considerably, an attempt was made to use doses which have been reported to be anticonvulsant in the rat against one or other convulsant procedure.Since many of the substances used are insoluble in any suitable media, some problems of uniform administration arose. After some preliminary experiments, the most satisfactory method was to weigh out the individual doses and suspend them as microcrystalline preparations for intraperitoneal injection. No attempts were made to determine the minimal effective dose or the duration of effect. The original dosage regimen was based on the previous study (Bonnycastle and Bradley, 1956) and usually consisted of four doses given over two days, the animals being

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This work was undertaken mainly in order to find a sensitive method for the assay of 5-hydroxytryptamine (HT) in tissue extracts. The biological test mostly used has been the contraction of oestrous rat uterus (Erspamer, 1942;Amin, Crawford, and Gaddum, 1954) (Bacq, Fischer, and Ghiretti, 1952). These preparations, however, were not found to be suitable for assay purposes. In the hands of Zetler and Schlosser (1954) Helix pomatia heart gave satisfactory results. Welsh (1953) found that Venus mercenaria (clam) heart-which had been earlier shown by him (Welsh, 1943) to be suitable for the quantitative estimation of acetylcholine (ACh) in tissue extracts-was stimulated by HT in low concentrations. This heart was used by Twarog and Page (1953) for the determination of HT in tissue extracts. The threshold concentration was 0.2-2 ttg./1. and the heart was relatively insensitive to other substances except ACh, the effect of which can, however, be blocked by benzoquinonium (Mytolon) (Luduefia and Brown, 1952), which is used clinically to paralyse voluntary muscles.Of preparations from different marine invertebrates found on the south coast of Britain, Welsh (1954) suggested the hearts of Cyprina islandica and Buccinum undatum as the most promising for HT and ACh bioassays. The heart of the freshwater mussel, Anodonta cygnea, also reacts to HT with graded responses (Fange, 1955).As mentioned above ACh is active on molluscan hearts and the usual response is inhibition. Recently Pilgrim (1954) has studied the action of ACh on the heart of a number of lamellibranch molluscs and Hughes (1955) has described Mya arenaria as a sensitive preparation for the assay of ACh. Adrenaline has been reported to stimulate some molluscan hearts in low concentrations, but has often been found quite ineffective. The results of different workers even on the same species have been different. For further information about the pharmacology of the molluscan heart the review of Krijgsman and Divaris (1955) may be consulted. These preparations are sometimes surpris--ingly different from the vertebrate heart or plain muscle.This paper describes the actions of certain drugs on the isolated hearts of various molluscs living in the sea near Britain, on the hearts of two snails (Helix aspersa and H. pomatia), and on preparations of Lumbricus terrestris. The heart of the bivalve, Spisula soida-formerly known as Mactra solida-was found most useful, because of the relative abundance and hardiness of the animal, the constancy of its heart over long periods and its sensitivity to HT. It has the advantage for workers in Great Britain that it is much more easily available that Venus mercenaria. METHODSIn most of the experiments the heart was suspended at room temperature (13-21°C.) in a 2 ml. bath, the contents of which could be changed by overflow, so that the mechanical disturbance was small. The heart of Buccinum was cannulated with a Straub cannula through the aorta and the auricle was tied off. Air was always bubbled through the fluid and the movement...

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