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We studied the effect of local administration of nicotine on the release of monoamines in striatum, substantia nigra, cerebellum, hippocampus, cortex (frontal, cingulate), and pontine nucleus and on the release of glutamic acid in striatum of rats in vivo, using microdialysis for nicotine administration and for measuring extracellular amine and glutamic acid levels. Following nicotine administration the extracellular concentration of dopamine increased in all regions except cerebellum; serotonin increased in cingulate and frontal cortex; and norepinephrine increased in substantia nigra, cingulate cortex, and pontine nucleus. Cotinine, the major nicotine metabolite, had no effect at similar concentrations. The cholinergic antagonists mecamylamine and atropine, the dopaminergic antagonists haloperidol and sulpiride, and the excitatory amino acid antagonist kynurenic acid all inhibited the nicotine-induced increase of extracellular dopamine in the striatum. The fact that kynurenic acid almost completely prevented the effects of nicotine, and nicotine at this concentration produced a 6-fold increase of glutamic acid release, suggests that the effect of nicotine is mainly mediated via glutamic acid release.

IN RECENT studies of glutamic acid metabolism in uivo, the fate of tracer amounts of rqlabelled glutamic acid administered intravenously to rats and mice was investigated in experiments of short duration (LAJTHA, BERL and WAELSCH, 1959). The major portion of the amino acid apparently entered brain, liver, kidney and muscle as the acid and conversion to the amide was not an essential prerequisite for exchange across the blood-brain barrier. The metabolic changes which then ensued were quite rapid, for within 2 min after injection of [14C]glutamic acid, the glutamic acid, gluta-EXPERIMENTAL Material. Uniformly labelled ["Clglutamic acid (1 1 pclpmole) and uniformly labelled [W]aspartic acid (5 pc/pmole) were obtained from Nuclear Chicago Corp. Uniformly labelled [*'C]glutamine (0.93 pc/pmole) was obtained from Merck and Co. of Canada. The purity of the labelled compounds was tested by column and paper chromatography. Animal and organ preparations Intracisterml injection of rat. Sprague-Dawley rats approximately 100 g in weight were used. Under light ether anaesthesia 0.02 ml of a neutralized amino acid solution was injected in the midline The abhreviations used are: GSH, glutathione; GABA, y-aminobutyric acid; TCA, trichloroacetic acid