Stimulation of Brain Serotonin Synthesis by Dibutyryl‐cyclic Amp in Rats

Tagliamonte, A.; Tagliamonte, P.; Forn, J.; Pérez-Cruet, Jorge; Krishna, Gopal; Gessa, Gian Luigi

doi:10.1111/j.1471-4159.1971.tb00218.x

Cited by 44 publications

(14 citation statements)

References 11 publications

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“…Unlike the effect of a single injection, serum total tryptophan increased with significant increases in the con tents of brain tryptophan, 5-HT and 5-HIAA. These findings are in essential agreement with previous reports (8,15). Results are given as means ± S.E.…”

Section: Resultssupporting

confidence: 94%

“…However, it did not cause detectable changes in the brain contents of tryptophan, 5-HT and 5-HIAA. On the other hand, in agree ment with previous reports (8,15), our results showed that subacute treatment with lithi um increased the brain contents of tryptophan, 5-HT and 5-HIAA and serum total trypto phan. Fractionation of the serum total tryptophan showed, however, that free tryptophan decreased and tryptophan bound to serum protein increased.…”

Section: Discussionsupporting

confidence: 94%

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Effect of Lithium on Serum Tryptophan and Brain Serotonin in Rats

1974

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Abstract-The influence of lithium administration on brain serotonin metabolism and the serum tryptophan level in rats was investigated.The brain tryptophan, serotonin and 5-hydroxyindole acetic acid contents did not change after a single in jection of lithium, but did increase significantly after repeated injections. A single injection of lithium caused a marked decrease in the serum total tryptophan level, but did not change the ratio of free to albumin bound tryptophan.On the contrary, repeated injections of lithium caused a significant increase in serum total tryptophan, and decrease in the ratio of free to bound tryptophan.Addition of lithium ion to normal rat serum in vitro did not change the ratio of free to bound tryptophan. A single injection of lithium produced a marked rise in serum nonesterified fatty acid, which is known to affect the binding of tryptophan by albumin.Lithium salts have been reported to be effective in treatment of mania and are used prophylactically to reduce the frequency of episodes of mania and depression (1). It is not known how lithium exerts the psychotropic effect, although numerous biochemical effects of lithium have been reported, including effects on brain catecholamine metabolism (2, 3), and on the electrolyte balance of the body (4, 5).Conflicting results have been reported on the action of lithium on brain serotonin (5-HT) metabolism (6, 7). However, recently it was reported that chronic administration of lithium increases the content of brain tryptophan and thereby the rate of synthesis of 5-HT in the brain (8). On the other hand, it has been established that the rate of syn thesis of 5-HT in the brain is regulated principally by the level of free tryptophan in the plasma (9). The present study was undertaken to determine the effect of acute or subacute treat ment with lithium on the contents of brain 5-HT and serum total and free tryptophan. MATERIALS AND METHODSMale Sprague-Dawley rats weighing 150 to 170 g and 270 to 300 g were used. Lithi um carbonate was dissolved in water and adjusted to pH 7.3 with N-HC1. As acute treat ment, lithium was injected i.p. as a single dose of 5 mEq/kg. As subacute treatment, in jections of 2 mEq/kg i.p. were given twice daily for 5 days and animals were sacrificed 5 hr after the last injection. Control rats were injected with 5 and 2 mEq/kg of sodium chloride, respectively. Animals were sacrificed by decapitation and the brain quickly removed, homogenized and stored at -20'C until analyzed. Blood was collected in a

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Section: Resultssupporting

confidence: 94%

Section: Discussionsupporting

confidence: 94%

Effect of Lithium on Serum Tryptophan and Brain Serotonin in Rats

1974

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“…For example, pyrrolase can compete for tryptophan (Curzon & Green, 1971) and other amino acids can interfere with its uptake by the brain (Fernstrom & Wurtman, 1972b;Oldendorf, 1971). Finally, it is possible that drugs which influence cyclic AMP metabolism may affect brain tryptophan not only by altering lipolysis but also through cyclic AMP changes in brain membranes as Tagliamonte, Tagliamonte, Forn, Perez-Cruet, Krishna & Gessa (1971) report that cyclic AMP (albeit in pharmacological dosage) increases tryptophan uptake by brain slices in vitro.…”

Section: Discussionmentioning

confidence: 99%

Effects on Plasma and Brain Tryptophan in the Rat of Drugs and Hormones That Influence the Concentration of Unesterified Fatty Acid in the Plasma

Curzon¹,

Knott²

1974

British J Pharmacology

143

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1 The effects on tryptophan distribution and metabolism of drugs altering plasma unesterified fatty acid (UFA) concentration were investigated in the rat. 2 UFA and plasma free (i.e. ultrafilterable) tryptophan altered in the same direction. 3 Catecholamines and L-DOPA increased both plasma UFA and free tryptophan. L-DOPA also increased brain tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) but decreased brain 5-hydroxytryptamine (5-HT). 4 Aminophylline increased plasma UFA and free tryptophan and also brain tryptophan, 5-HT and 5-HIAA. Food deprivation had qualitatively similar effects. 5 Insulin decreased plasma UFA and free tryptophan in both fed and food-deprived rats. However, while in fed rats these changes were associated with small decreases of brain indoles, in food-deprived animals small increases occurred. 6 Nicotinic acid had only small effects in fed rats but it opposed both the UFA and indole changes in food-deprived animals. Total plasma tryptophan increased in nicotinic acid treated, food-deprived rats. 7 There was a tendency towards inverse relations between changes of plasma free and total tryptophan. 8 The results suggest that drugs which influence plasma UFA through actions on cyclic AMP thereby alter the binding of tryptophan to plasma protein and that this leads to altered distribution and metabolism of tryptophan.

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“…This exhibits diurnal variations and may be affected by the activity of central catecholaminergic systems (Hery, Rouer, Kan & Glowinski, 1974) and cyclic adenosine-3 ',5 '-monophosphate (cyclic AMP) (Tagliamonte, Tagliamonte, Forn, Perez-Cruet, Krishna & Gessa, 1971).…”

Section: Introductionmentioning

confidence: 99%

Effect of Aminophylline on Tryptophan and Other Aromatic Amino Acids in Plasma, Brain and Other Tissues and on Brain 5‐hydroxytryptamine Metabolism

Curzon

Fernando

1976

British J Pharmacology

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1Aminophylline and other methylxanthines increase brain tryptophan and hence 5-hydroxytryptamine turnover. The mechanism of this effect of aminophylline was investigated. 2 At lower doses (t> 100 mg/kg i.p.) the brain tryptophan increase could be explained by the lipolytic action of the drug, i.e. increased plasma unesterified fatty acid freeing plasma tryptophan from protein binding so that it became available to the brain. 3 Plasma unesterified fatty acid did not increase when aminophylline (100 mg/kg i.p.) was given to nicotinamide-treated rats but as both plasma total and free tryptophan rose, a tryptophan increase in the brain still occurred. 4 The rise in brain tryptophan concentration following the injection of a higher dose of the drug (150 mg/kg i.p.) could no longer be explained by a rise of plasma free tryptophan as the ratio of brain tryptophan to plasma free tryptophan rose considerably. Plasma total tryptophan fell and the plasma insulin concentration rose. 5The increase of brain tryptophan concentration after injection of 150 mg/kg aminophylline appeared specific for this amino acid as brain tyrosine and phenylalanine did not increase. However as their plasma concentrations fell the brain/plasma ratio for all three amino acids rose. 6 The higher dose of aminophylline increased the muscle concentration of tryptophan but that of tyrosine fell and that of phenylalanine remained unaltered. The liver concentrations were not affected. 7 The aminophylline-induced increases of the ratio of brain tryptophan to plasma free tryptophan no longer occurred when the drug was given to animals injected with the fl-adrenoceptor blocking agent propranolol or the diabetogenic agent streptozotocin. 8 The changes in brain tryptophan upon aminophylline injection may be explained by (a) increased availability of plasma tryptophan to the brain due to increased lipolysis and (b) increased effectiveness of uptake of tryptophan by the brain due to increased insulin secretion.

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Stimulation of Brain Serotonin Synthesis by Dibutyryl‐cyclic Amp in Rats

Cited by 44 publications

References 11 publications

Effect of Lithium on Serum Tryptophan and Brain Serotonin in Rats

Effect of Lithium on Serum Tryptophan and Brain Serotonin in Rats

Effects on Plasma and Brain Tryptophan in the Rat of Drugs and Hormones That Influence the Concentration of Unesterified Fatty Acid in the Plasma

Effect of Aminophylline on Tryptophan and Other Aromatic Amino Acids in Plasma, Brain and Other Tissues and on Brain 5‐hydroxytryptamine Metabolism

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