Brain Tryptophan Concentrations Research Articles

Route of Administration of Tryptophan and Tyrosine Affects Short-Term Food Intake and Plasma and Brain Amino Acid Concentrations in Rats ,

The effects of route of administration of tryptophan and tyrosine on food intake and diet selection and on plasma and brain tryptophan or tyrosine concentrations were studied. Tryptophan and tyrosine given intraperitoneally at 100 mg/kg body wt suppressed food intake by 33–45% over a 2-h feeding period beginning 30 min after injections. No preferential effect was shown for either the high carbohydrate or high protein diet choice. When given intragastrically at this dose, neither tryptophan nor tyrosine affected food intake. Tryptophan, but not tyrosine, at 200, 400 and 600 mg/kg body wt given intragastrically reduced food intake and carbohydrate diet intake by an average of 20 and 25%, respectively, in the first 2 h of feeding. Plasma and brain tryptophan were higher for 30 min following intraperitoneal tryptophan injections than after tryptophan given intragastrically at 100 mg/kg body wt. However, intraperitoneal tyrosine (100 mg/kg body wt) resulted in higher plasma tyrosine levels at 5–10 min but lower levels at 30 min than when tyrosine was given intragastrically. Brain tyrosine was higher after intraperitoneal treatment only at 10 min and was similar to intragastric treatment at other times. When these amino acids were given intragastrically at 400 mg/kg body wt, higher plasma tryptophan, plasma tyrosine and brain tyrosine were found than following intraperitoneal injection of the behaviorally effective dose (100 mg/kg body wt) at 30 min. Thus the reduced effect on food intake of tryptophan or tyrosine given intragastrically compared with intraperitoneally is not readily explained by their lower concentrations in plasma and brain preceding and at the time that the rats had access to food.

Effects of Tryptophan on Depression and Aggression in STZ-D Mice

Streptozocin-induced diabetic (STZ-D) mice have reduced brain concentrations of tryptophan, a precursor substance for 5-hydroxytryptamine, and show lengthened immobility in Porsolt's swim test, a putative animal model of depression. This study investigated whether tryptophan affects behavior in Porsolt's swim test in STZ-administered male National Institutes of Health Swiss mice. In addition, the effect of tryptophan on behavior in the resident-intruder test of aggression was studied. Tryptophan is effective in the treatment of mild depression and may reduce aggressive behavior. Diabetes was induced with injection of 200 mg/kg body wt i.p. STZ. Two weeks after STZ treatment, the mice received 0, 50, and 100 mg/kg i.p. tryptophan 60 min before the swim test. The STZ-administered mice exhibited lengthened immobility in the swim test, and tryptophan caused a dose-related shortening in their immobility times. The control and STZ mice, which were isolated for 1 wk before the resident-intruder test, did not show any difference in the time spent in social investigation or aggressive or defensive behaviors. However, 100 mg/kg i.p. tryptophan 60 min before the test reduced the social interaction and aggressive behavior of the STZ-D mice but increased these behaviors in controls. Results indicate that tryptophan shortens the increased immobility time and reduces social and aggressive behavior in STZ-D mice. Therefore, the reported reductions in the brain-tryptophan concentrations in STZ-D mice may participate in regulating their behavior.

Photosensitized Oxidation of Tryptophan: Effect on Liver and Brain Tryptophan

Toxic products are formed when tryptophan is irradiated with light in the presence of photosensitizers such as riboflavin. In order to further investigate this phenomenon, solutions of tryptophan (48 mumol.mL-1) were irradiated with broad spectrum fluorescent light in the presence or absence of riboflavin (0.01 mg.mL-1). Solutions of riboflavin were similarly irradiated; control solutions were the respective solutions not exposed to light. Two-week-old suckling gerbils were then assigned to receiving 7 days of intraperitoneal injections of the light-exposed or non-light-exposed solutions. There were significant differences in the concentrations of tryptophan in serum, liver, and brain; activity of gamma-glutamyl transferase (GGT) as well as liver protein were also significantly different among the groups. Body and liver weights were also significantly different among the groups. In order to identify the photoproducts responsible for these changes, solutions of tryptophan that had been irradiated with light in the presence of riboflavin were then fractionated based on time of elution during high-pressure liquid chromatography and the fractions were then injected into the gerbils as before. GGT responses to one of the fractions was similar to that of the parent compound. Chromatographic studies indicated the presence of numerous photoadduct compounds of tryptophan and riboflavin after exposure to light. Both the presence of riboflavin and the exposure of the solutions to light alter brain concentrations of tryptophan in the developing gerbil indicating differing availability to the brain of this serotonin precursor. Clinical implications of the infusion of amino acids in the presence of photosensitizers and light must be considered.

Development of Tolerance to the Plasma Amino Acid-Decreasing Effect of Ethanol in the Rat

Male Sprague-Dawley rats were treated for one month with daily intraperitoneal injections of ethanol (2 g kg-1), or saline. After this pretreatment, animals from each group were given acute doses of ethanol (2 g kg-1) or saline. Plasma amino acid concentrations and brain tyrosine, tryptophan, dopamine, 5-HT and 5-HIAA concentrations were measured in samples collected 1 h after the injections. Acute administration of ethanol induced a dramatic fall in the concentrations of 18 out of 20 plasma amino acids in animals pretreated with saline. In animals chronically pretreated with ethanol this decrease was much smaller. Furthermore, the decrease was significantly lower for 6 of the measured amino acids in the chronic ethanol group compared with the saline-treated control group. Tolerance to the plasma amino acid decreasing effect of ethanol had thus developed. This acquired tolerance might be explained by both pharmacokinetic and pharmacodynamic mechanisms. Chronic administration of ethanol induced increased concentrations of tyrosine and dopamine in the brain, probably due to increased transport of tyrosine into the brain caused by an increase in the ratio of tyrosine to large neutral amino acids in plasma.

The effects of lofepramine and desmethylimipramine on tryptophan metabolism and disposition in the rat

Acute and chronic administration of lofepramine and its major metabolite desmethylimipramine (DMI) to rats elevates brain tryptophan concentration, thereby enhancing cerebral 5-hydroxytryptamine (5-HT) synthesis, by increasing the availability of circulating tryptophan to the brain, secondarily to inhibition of liver tryptophan pyrrolase (tryptophan 2,3-dioxygenase, l-tryptophan:O 2 oxidoreductase, decyclizing; EC 1.13.11.11) activity. The pyrrolase inhibition by lofepramine occurs independently of metabolism to DMI, because it can be demonstrated directly in vitro. Lofepramine also differs from DMI in its action profile on the above and related aspects of tryptophan metabolism and disposition. These results demonstrate that lofepramine influences tryptophan and 5-HT metabolism and disposition independently of its major metabolite DMI, and are discussed briefly in relation to the mechanism of action of antidepressants.

Effects of acute paroxetine administration on tryptophan metabolism and disposition in the rat

1 The effects of acute oral administration of paroxetine on tryptophan metabolism and disposition were examined in the rat. 2 Basal liver tryptophan pyrrolase activity was inhibited by paroxetine in vitro and after oral administration. Maximum inhibition was caused by a 1 mg kg-1 dose. 3 Paroxetine administration also inhibited pyrrolase activity that had previously been enhanced by hormonal induction by cortisol or cofactor activation by haematin. The cortisol induction of the enzyme was, however, not inhibited by pretreatment of rats with paroxetine. 4 Paroxetine increased tryptophan availability to the brain, because of the above pyrrolase-inhibitory mechanism. Cerebral 5-hydroxytryptamine (5-HT) synthesis was accordingly enhanced, though this was apparent only with doses of the drug of up to 1 mg kg-1. With larger doses, decreased 5-HT turnover, probably as a result of 5-HT uptake inhibition, was the more dominant feature. 5 Paroxetine lowered circulating corticosterone concentration, but did not influence those of albumin, non-esterified fatty acids or glucose. 6 It is concluded that, in addition to inhibiting brain 5-HT turnover, paroxetine also, in common with 20 other antidepressants, enhances 5-HT synthesis by increasing brain tryptophan concentration secondarily to inhibition of liver tryptophan pyrrolase activity.

Hyperammonaemia causes many of the changes found after portacaval shunting

1. Portacaval shunting in rats results in several metabolic alterations similar to those seen in patients with hepatic encephalopathy. The characteristic changes include: (a) diminution of cerebral function; (b) raised plasma ammonia and brain glutamine levels; (c) increased neutral amino acid transport across the blood-brain barrier; (d) altered brain and plasma amino acid levels; and (e) changes in brain neurotransmitter content. The aetiology of these abnormalities remains unknown. 2. To study the degree to which ammonia could be responsible, rats were made hyperammonaemic by administering 40 units of urease/kg body weight every 12 h and killing the rats 48 h after the first injection. 3. The changes observed in the urease-treated rats were: (a) whole-brain glucose use was significantly depressed, whereas the levels of high-energy phosphates remained unchanged; (b) the permeability of the blood-brain to barrier to two large neutral amino acids, tryptophan and leucine, was increased; (c) blood-brain barrier integrity was maintained, as indicated by the unchanged permeability-to-surface-area product for acetate; (d) plasma and brain amino acid concentrations were altered; and (e) dopamine, 5-hydroxytryptamine (serotonin) and noradrenaline levels in brain were unchanged, but 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of 5-hydroxytryptamine, was elevated. 4. The depressed brain glucose use, increased tryptophan permeability-to-surface-area product, elevated brain tryptophan content and rise in the level of cerebral 5-HIAA were closely correlated with the observed rise in brain glutamine content. 5. These results suggest that many of the metabolic alterations seen in rats with portacaval shunts could be due to elevated ammonia levels. Furthermore, the synthesis or accumulation of glutamine may be closely linked to cerebral dysfunction in hyperammonaemia.

Distribution of 5-hydroxytryptamine and related compounds in various brain regions of rainbow trout (Oncorhynchus mykiss)

The levels of tryptophan (Try), 5-hydroxytryptamine (serotonin, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the brain regions of rainbow trout (Oncorhynchus mykiss) by high performance liquid chromatography with electrochemical detection (HPLC-EC). Brain tryptophan concentrations varied from 3.972 ± 357 ng/g cerebellum) to 8.841 ± 772 ng/g (hypothalamus). The 5-HT concentrations varied from 69 ± 7 ng/g (optic tectum) to 573 ± 34 ng/g (hypothalamus). The concentrations of 5-HIAA varied from 29 ± 3 ng/g (medulla oblongata) to 68 ± 7 ng/g (hypothalamus). Total and free serum tryptophan levels were also determined; in adult rainbow trout 92% of the serum tryptophan was observed to be free i.e., not protein-bound.

Heme precursor 5-aminolevulinic acid alters brain tryptophan and serotonin levels without changing pineal serotonin and melatonin concentrations.

The daytime administration of the heme precursor 5-aminolevulinate (5-ALA) has been shown to reduce brain tryptophan and serotonin levels owing to saturation of liver tryptophan pyrrolase. Saturation of this enzyme with heme results in enhanced activity, leading to increased catabolism of tryptophan and thus making less tryptophan available to the brain. Tryptophan is also the precursor of melatonin, a primary secretory product of the pineal gland. Reduced melatonin levels, which could be a consequence of altered tryptophan metabolism, have been associated with depressive disorders in humans. In view of this, in the present study we examined the effects of 5-ALA administration on forebrain tryptophan and serotonin levels as well as pineal serotonin, melatonin, and the pineal melatonin-forming enzymes N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). 5-ALA induced a reduction in forebrain tryptophan and serotonin levels during the light phase and caused the opposite effect in the dark phase. Allopurinol, an inhibitor of hepatic tryptophan pyrrolase activity, prevented the reduction in the indole levels induced by 5-ALA. Although 5-ALA induced these changes in the forebrain, it did not alter either daytime or nighttime pineal NAT, HIMOT, serotonin, or melatonin levels. It appears that high serotonin levels and melatonin production in the pineal are conserved even in the face of low circulating tryptophan levels, changes which alter brain tryptophan and serotonin concentrations.

Comparative effects of carbohydrate restriction vs starvation on biochemical parameters related to neurotransmitters in rat.

Adult rats were submitted to a 4-day starvation period or maintained on a 50% carbohydrate-restricted diet for 8 consecutive days to obtain a body weight loss of 20-30%. Serum dopamine-beta-hydroxylase (DBH) activity and amino acids content were measured as well as brain tryptophan and tyrosine levels. Moreover, brain serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA), and dopamine (DA) contents were assayed in five brain areas. In 4-day starved and 8-day carbohydrate-restricted rats, the serum tyrosine and total tryptophan contents as well as tyrosine to the sum of six neutral amino acids ratios were lowered. Moreover, in these groups, free tryptophan to the sum of six neutral amino acids ratio remained normal and serum DBH activity increased. In the brain, to a decreased tyrosine content observed in 4-day starved and 8-day carbohydrate-restricted rats corresponded a high DA to NA ratio in the hypothalamus, thalamus, and raphe nuclei, thus suggesting a low DA utilization whereas a low DA to NA ratio was found in the neostriatum. On the other hand, brain tryptophan content was decreased in 4-day starved rats and increased in 8-day carbohydrate-restricted rats. In the former group, a high 5-HT to 5-HIAA ratio characteristic of a low 5-HT utilization was found in the hypothalamus and neostriatum whereas in the latter group a significant decrease in this ratio was only observed in the thalamus. These results suggest that the biochemical response to starvation vs carbohydrate restriction can be differentiated on neurochemical and neuroanatomical bases.

In vivo evidence for a greater brain tryptophan hydroxylase capacity in female than in male rats

Previous studies have revealed that brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) are moderately higher in female than in male rats. Since tryptophan hydroxylase is only about half saturated with substrate, the greater availability of precursor in female rats might contribute to their higher 5-hydroxyindole levels. The present investigation was aimed at clarifying whether there is a sex difference in central tryptophan hydroxylase capacity. Hence, both sexes received a high dose of L-tryptophan (400 mg/kg), which resulted in a tenfold increase in brain tryptophan concentrations and presumably a virtual saturation of tryptophan hydroxylase. Following such treatment, 5-hydroxytryptophan (5-HTP) levels, measured after L-amino acid decarboxylase inhibition, were compared in males and females. Both in saline- and L-tryptophan-treated rats, 5-HTP levels were generally higher in females. In another group of animals, receiving 400 mg/kg of L-tryptophan as sole treatment, 5-HT and 5-HIAA concentrations were measured. As in the case of 5-HTP, the higher 5-HT and 5-HIAA levels observed in females persisted after L-tryptophan treatment. The present data suggest that brain tryptophan hydroxylase activity is greater in females; this sex difference probably contributes to the higher 5-HT and 5-HIAA levels in females.

Effect of acute oral doses of T-2 toxin on tissue concentrations of biogenic amines in the rat.

T-2 toxin [3 alpha-hydroxy-4 beta, 15-diacetoxy-8 alpha-(3-methylbutyryloxy)-12,13-epoxytrichotec-9-ene] is an emetic Fusarium trichothecene mycotoxin known to cause lethargy, ataxia and feed refusal in economically important animals. Experiments were conducted to determine the effect of acute oral doses of T-2 toxin on tissue concentrations of neurotransmitters thought to play some role in regulation of feed consumption. Sixty-seven male weanling rats were intubated with a few grams of diet in a liquid slurry with or without 2.0 mg T-2 toxin per kilogram of body weight. At 1, 2, 4, 6, 8, 12, 24 and 48 h following dosing, rats were killed, and brains, spleens, hearts and adrenal glands were excised and analyzed for concentrations of neurotransmitters and metabolites using high-performance liquid chromatography with electrochemical detection. Administration of T-2 toxin caused increases in brain concentrations of tryptophan and serotonin at the early time intervals after dosing. Brain concentrations of dopamine increased, whereas concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) decreased at the later time interals following dosing. Concentrations of dopamine were increased in adrenal glands, whereas epinephrine concentrations decreased. Epinephrine was detected in spleen and heart after administration of T-2 toxin. It was concluded that the increase in brain indoleamines induced by T-2 toxin could contribute to feed refusal in animals suffering from T-2 toxicosis.

Observations on predicted brain influx rates of neurotransmitter precursors. Effects of tumor, operative stress with tumor removal, and postoperative TPN of varying amino acid compositions.

Effects of tumor, operative stress and tumor removal, and postoperative TPN of varying amino acid compositions on brain levels of tryptophan or tyrosine as predicted by their brain influx rates were studied in normals and in malnourished cancer patients. Concentrations of the large neutral amino acids (LNAA) were determined in patients before and after tumor removal, and in postoperative patients before and after receiving either a standard TPN solution (STD-TPN), or a branched-chain amino acid solution (BCAA-TPN). The LNAA were altered in all groups versus normals. Brain influx rates showed the following: in preoperative patients, predicted brain tryptophan levels were below normal (P less than 0.001), whereas tyrosine levels were within or above normal; no significant differences between pre- and postoperative tryptophan or tyrosine levels; postoperative STD-TPN did not change predicted brain tryptophan concentration from preinfusion values, but BCAA-TPN decreased it (P less than 0.001), underscoring the common transport carrier; and preinfusion predicted brain tyrosine levels were decreased (P less than 0.001) by both types of TPN solutions. These results imply low substrate levels for brain serotonin and catecholamine synthesis, possibly affecting functions dependent on their control.

Inhibition of rat Liver Tryptophan Pyrrolase Activity and Elevation of Brain Tryptophan Concentration by Administration of DL-α-Amino-β-Pyridinepropanoic Acid (Pyridylalanine) Analogs

Single doses of DL-alpha-amino-beta-(2-pyridine)propanoic acid (2-PA, 100 mg/kg) significantly decreased the holoenzyme and apoenzyme activities of rat liver tryptophan pyrrolase (TP) and increased brain tryptophan, serotonin (5-HT) and 5-hydroxyindole-3-ylacetic acid concentrations. 2-PA had no inhibitory effect on either of the enzyme activities in vitro, but its expected metabolites were effective. Single doses of DL-alpha-amino-beta-(3-pyridine)propanoic acid (3-PA, 100 mg/kg) decreased only the holoenzyme activity and elevated brain tryptophan and its metabolites levels in rats. 3-PA and its metabolite, 3-pyridylpyruvate, inhibited only the holoenzyme activity in vitro. DL-alpha-Amino-beta-(4-pyridine)propanoic acid (4-PA) caused significant changes in liver TP (holo- and apoenzyme forms) activity and brain tryptophan concentration only after repeated administration (100 mg/kg/day). 4-PA was a weak inhibitor of the holoenzyme, but its metabolites apparently inhibited the holo- and apoenzyme activities in vitro. These findings suggest that PA analogs (and/or their metabolites) increased brain tryptophan (and hence 5-HT synthesis) by directly inhibiting liver TP activity.

Effect of sustained exercise on concentrations of plasma aromatic and branched-chain amino acids and brain amines

In both trained and untrained rats, exercise increased the plasma concentration ratio of aromatic amino acids to branched-chain amino acids which might favour entry of the aromatic amino acids into the brain. Exercise in trained rats did not change the brain concentration of 5-hydroxytryptamine but increased that of 5-hydroxyindole acetic acid. Exercise in the untrained rat increased the concentration of brain tryptophan and that of 5-hydroxytryptamine but that of 5-hydroxyindole acetic acid was unchanged. The increased concentration of 5-hydroxytryptamine in untrained rats might be involved in central fatigue.

Audiogenic seizures and brain serotonin after l-tryptophan and p-chlorophenylalanine

Despite intense investigation, the role of serotonergic neurons in audiogenic seizures in mice remains uncertain. In the work reported here, audiogenic seizure susceptibility and brain tryptophan and serotonin concentrations were measured in DBA 2J mice after administration of three doses of l-tryptophan or p-chlorophenylalanine. p-Chlorophenylalanine reduced brain serotonin and significantly prolonged the latency to appearance of all seizure phases. l-tryptophan was largely ineffective in protecting against seizures and in elevating brain serotonin content, despite the fact that it caused a marked increase in brain tryptophan content. Thus, it appears that DBA 2J mice have an impaired ability to synthesize serotonin from tryptophan.

Absence of Chronic Effects of Dietary Protein Content on Brain Tryptophan Concentrations in Rats

Groups of young, adult, male rats were given free access for 2 wk to a diet containing 12, 24 or 40% protein (dry weight). During this period, all animals grew considerably; those consuming the 12% protein diet grew less rapidly than those ingesting the higher percent protein diets. At the end of 2 wk, six rats from each diet group were killed every 4 h throughout a 24-h period, and blood samples and whole brains were obtained for analysis. Serum tryptophan levels were lowest in animals consuming the 12% protein diet, intermediate in rats consuming the 24% protein diet and highest in rats consuming the 40% protein diet (at all times studied). Brain tryptophan levels, however, did not differ significantly as a function of dietary protein content. The ratio in serum of the concentration of tryptophan to the sum of the concentrations of its competitors for brain uptake also was not significantly influenced by dietary protein level. Levels of 5-hydroxyindoles in brain showed significant diurnal variations but no evidence of a significant effect of dietary protein content. Since the ratio of serum tryptophan to its competitors and the levels in brain of tryptophan and 5-hydroxyindoles did not vary as a function of dietary protein intake, the results do not support the view that these variables serve as signals to the brain for regulating longterm dietary protein intake.

3,4‐Dihydroxyphenylethylamine and 5‐Hydroxytryptamine Metabolism in the Rat: Acidic Metabolites in Cisternal Cerebrospinal Fluid Before and After Giving Probenecid

3,4-Dihydroxyphenylethylamine (DA, dopamine) and 5-hydroxytryptamine (5-HT) turnover values were determined in freely moving male rats by measuring the rates of accumulation of the acidic metabolites of the above transmitters, i.e., 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in cisternal cerebrospinal fluid (CSF) samples after probenecid (200 mg/kg i.p.) administration. Determinations on samples before and after acid hydrolysis showed that the latter procedure was necessary for DA turnover determination. Thus whereas total (DOPAC + HVA) increased linearly with time after probenecid, free (DOPAC + HVA) did not. This was because the percentage of DOPAC + HVA in conjugated form increased with time. Determinations on a group of 28 rats during the dark (red light) period showed that cisternal amine metabolite concentrations before probenecid injection did not parallel turnover values. This was probably because individual differences in metabolite egress strongly affect the pre-probenecid values. The poor correlations between CSF tryptophan and 5-HT turnover suggested that differences of brain tryptophan concentration were not major determinants of differences of brain 5-HT metabolism within this group of normal rats. Considering that the rats were of similar weight and that the turnover values were all determined at approximately the same time of day, the three- to fourfold ranges of the turnover values are remarkable. The positive correlation between the DA and 5-HT turnovers of individual rats suggests the existence of common effects on DA and 5-HT turnover in normal rats.

Variables influencing the effect of a meal on brain tryptophan.

Previous work from our laboratory points to plasma free tryptophan being a useful predictor of brain tryptophan concentration in many circumstances. Other work, in particular various studies on the acute effects of food intake, has emphasized the roles of plasma total tryptophan and of plasma large neutral amino acids that compete with tryptophan for transport to the brain. We have now studied associations between the above variables under different dietary conditions. Rats were allowed to feed for restricted periods during a 12-h light-12-h dark cycle. In the first study, rats were given access to a carbohydrate diet for 2 h midway through the light cycle and following an 18-h fast. The resultant rise of brain tryptophan was explicable largely by the associated fall in large neutral amino acids. In a second study, rats were adapted to a regimen whereby they were allowed access to the standard laboratory diet for 4 h during the dark cycle for 3 weeks. A postprandial decrease in brain tryptophan was associated with a fall in free tryptophan and of its ratio to competing amino acids. The brain change could be attributed neither to changes in plasma total tryptophan (which increased) nor to changes of its ratio to the competers (which remained unchanged). Results as a whole are thus consistent with changes of plasma free tryptophan and large neutral amino acid concentrations affecting brain tryptophan concentration under different dietary circumstances. It is suggested that these influences serve to maintain brain tryptophan when dietary supplies are defective.

Spontaneous motor activity increases after portacaval anastomosis in rats

Spontaneous motor activity was monitored in rats at various times, up to 14 weeks, after portacaval anastomosis (PCA) or sham operation. Total 24 hour activity scores rose significantly after PCA and remained significantly higher than those of sham operated rats for twelve weeks. After PCA, activity during the twelve hour lighted period was greatly increased, whereas dark period activity was unchanged. Increased activity in the light period was found to be well correlated with the degree of elevation in brain concentrations of tryptophan, tyrosine, phenylalanine and glutamine. These results are consistent with previously reported EEG studies and suggest that motor-activity measurement may facilitate the correlation of biochemical changes with behaviour in rats with portal systemic shunting.