The anticonvulsant properties of adenosine were tested pharmacologically on amygdala-kindled seizure activity in rats. The adenosine analogue 2-chloroadenosine and the adenosine uptake blocker papaverine both increased the latency to behavioral clonus as well as reduced the duration and severity of the clonic motor convulsion. Both drugs, however, failed to alter the postkindling afterdischarge (AD) threshold. Theophylline, an adenosine antagonist, had the opposite effects, prolonging the AD and motor seizure durations and facilitating partially kindled seizures, but again not altering the prekindling or postkindling AD thresholds of amygdala-elicited seizures. In contrast, carbamazepine raised AD thresholds, suggesting that it does not produce its anticonvulsant effects through adenosine systems. Since endogenous adenosine can impede seizure spread and seizure continuation, but does not affect seizure initiation from the amygdala, perhaps endogenous adenosine has the special property of being brought into play as an anticonvulsant only by the seizure itself.

Changes in biogenic amine levels associated with the morphological and behavioural development of the worker honeybee are examined. A significant increase in amine levels in the head of the honeybee is associated with transition from the larval to pupal stage. Adult emergence is also accompanied by a significant increase in 5-HT levels in the brain, but no significant change in brain dopamine (DA) levels. NADA (N-acetyldopamine) levels increase during larval and pupal development, but in contrast to both DA and 5-HT, drop significantly during the transition from pupa to adult. Levels of DA in the brain of nectar and pollen forager bees, presumed to be among the oldest adults sampled, were found to be significantly higher than in nurses, undertakers or food storers. These results suggest that an age-dependent change in amine levels occurs in the brain of the worker bee. In the optic lobes, levels of DA and 5-HT were found to be significantly higher in pollen forager bees than in all other behavioural groups. Significant differences in amine levels in the optic lobes of nectar foragers and pollen foragers indicate that some differences in amine levels occur independent of worker age. The functional significance of differences in brain amine levels and whether or not biogenic amines play a direct role in the control of honeybee behaviour has yet to be established.

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There have been a number of studies of the effects of drugs on the content of various amines found in brain tissue. In particular, the concentrations in the brain of noradrenaline (Vogt, 1954) and 5-hydroxytryptamine (Paasonen & Vogt, 1956;Brodie, Shore & Pletscher, 1956) have been determined before and after treatment with drugs, and many attempts have been made to correlate the change in brain amine concentration with an observable change in animal behaviour. Later, brain dopamine (3,4-dihydroxyphenylethylamine) has been included in such studies (Bertler, 1961).In the present experiments, the content of dopamine, noradrenaline and 5-hydroxytryptamine in different parts of cat and dog brain was measured, and so was the content of homovanillic acid (4-hydroxy-3-methoxyphenylacetic acid) and 5-hydroxyindol-3-ylacetic acid, the major acid metabolites of dopamine and 5-hydroxytryptamine. The corresponding acid metabolite of noradrenaline, vanillylmandelic acid (4-hydroxy-3-methoxymandelic acid), has not been detected in brain tissue (Anden, Roos & Werdinius, 1964; Sharman, unpublished) and so could not be determined. The simultaneous determination of an amine and its metabolite permitted a study of the effect of the drug not only on the content of the amine but also on a possible indicator of the rate of metabolism of the amine.The concentrations of both dopamine and homovanillic acid are highest in the brain in the caudate nucleus and putamen; since the caudate nucleus is easy to dissect out reproducibly it was used for the estimation of these two compounds. The caudate nucleus is thought to form part, with other basal ganglia which also contain dopamine, of the " extrapyramidal motor system", though recent evidence suggests that it has a more generalized function, acting as an integrative centre for the whole of the cortex (Laursen, 1963;Carman, Cowan & Powell, 1963 (Laverty, 1963;Sharman, 1963b (1958). The column was fitted with a capillary tube which maintained a flow rate of 8 to 10 ml./hr without applied pressure. When the supernatant fluid had run through, the column was washed with 4 ml. of water; then the noradrenaline was eluted with 8 ml. of 0.4 N-hydrochloric acid. A further fraction which contained dopamine could be obtained by eluting with 8 ml. of 2 N-hydrochloric acid. The columns used for caudate nucleus extracts were washed with 6 ml. of 0.4 N-hydrochloric acid instead of water to remove any noradrenaline or dihydroxyphenylalanine, and the dopamine was eluted with 8 ml. of 2 N-hydrochloric acid.Edetic acid disodium salt (20,.tg) was added to the dopamine eluates which were then brought to pH 4 with solid sodium bicarbonate.Noradrenaline in the eluates was determined fluorimetrically by a ferricyanide oxidation method (Sharman, Vanov & Vogt, 1962). The fluorescence was measured using a Locarte filter fluorimeter with a Chance OX1 primary filter, and an Ilford 625 secondary filter. This filter combination gave equivalent fluorescence with equal amounts of noradrenaline and adrenaline; the result...