Dependence of 5-HT and catecholamine synthesis on concentrations of precursor amino-acids in rat brain

Carlsson, Arvid; Lindqvist, Margit

doi:10.1007/bf00508062

Cited by 315 publications

(170 citation statements)

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“…Scally et al (1977) were the first to demonstrate that exogenous tyrosine could potentiate haloperidol-induced increases in striatal DA metabolites, suggesting an increase in DA utilization (Scally et al 1977). These results were confirmed by others who found that exogenous tyrosine augmented the haloperidol-induced increase in striatal DOPA accumulation (Carlsson and Lindqvist 1978;Westerink and Wirix 1983). Tyrosine-induced potentiation of DA synthesis, as suggested by changes in either DA metabolites or DOPA accumulation, was also reported after pretreatment with amfonelic acid, spiperone (Fuller and Snoddy 1982), reserpine (Sved et al 1979) or in animals with near total striatal DA depletion (Melamed et al 1980).…”

Section: Discussionmentioning

confidence: 65%

mentioning

confidence: 99%

“…The availability of tyrosine in the brain normally exceeds the capacity of the enzyme tyrosine hydroxylase (TH) to convert it to DOPA (Carlsson and Lindqvist 1978;Morgenroth et al 1976;Joh et al 1978). Since the conversion of DOPA to DA is rapid and efficient, DA synthesis usually depends on TH activity and not on tyrosine levels (Wurtman et al 1974;Carlsson and Lindqvist 1978). However, precursor dependence of DA synthesis has been demonstrated in the light-activated retina (Fernstrom et al 1984(Fernstrom et al , 1986 as well as in striatal DA neurons after administration of haloperidol, spiperone, reserpine or amfonelic acid (Scally et al 1977;Sved et al 1979;Fuller and Snoddy 1982) or after marked DA depletion (Melamed et al 1980).…”

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Tyrosine Augments Acute Clozapine- but not Haloperidol-Induced Dopamine Release in the Medial Prefrontal Cortex of the Rat An in vivo Microdialysis Study

Jaskiw

Collins

Pehek

et al. 2001

Neuropsychopharmacology

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Tyrosine availability can influence dopamine (DA) synthesis in highly electrophysiologically active DAergic neurons, such as those innervating the medial prefrontal cortex (MPFC).In most brain dopamine (DA) systems, levels of the DA precursor tyrosine do not significantly affect dopaminergic transmission. The availability of tyrosine in the brain normally exceeds the capacity of the enzyme tyrosine hydroxylase (TH) to convert it to DOPA (Carlsson and Lindqvist 1978;Morgenroth et al. 1976;Joh et al. 1978). Since the conversion of DOPA to DA is rapid and efficient, DA synthesis usually depends on TH activity and not on tyrosine levels (Wurtman et al. 1974;Carlsson and Lindqvist 1978). However, precursor dependence of DA synthesis has been demonstrated in the light-activated retina (Fernstrom et al. 1984(Fernstrom et al. , 1986 as well as in striatal DA neurons after administration of haloperidol, spiperone, reserpine or amfonelic acid (Scally et al. 1977;Sved et al. 1979;Fuller and Snoddy 1982) or after marked DA depletion (Melamed et al. 1980). The common feature of these paradigms is a marked increase in the electrophysiological activity of the relevant DA system. Such data suggest that precursor dependence of DA synthesis may be a latent property of all DA neurons, but one which emerges only under conditions of increased dopaminergic activity. (Chiodo et al. 1984;White and Wang 1984), precursor dependence of medial prefrontal cortical (MPFC) DA synthesis might be expected even under basal conditions. Even within the MPFC, however, tight feedback systems limit the ability of exogenous tyrosine administration to augment DA synthesis (Tam et al. 1990). Intriguingly, in rats pretreated with FG-7142, a beta-carboline known to preferentially increase MPFC synthesis, utilization and release Roth 1985, 1990;Bradberry et al. 1991), administration of tyrosine robustly enhances MPFC DA synthesis (Tam et al. 1990). We postulated that such precursor dependence would also be established by other drugs which activate mesocortical dopaminergic activity.The atypical and clinically superior antipsychotic drug, clozapine, has already been demonstrated to preferentially release DA in the prefrontal cortex of the rat (Moghaddam and Bunney 1990; Pehek and Yamamoto 1994;Yamamoto and Cooperman 1995) as well as of the non-human primate (Youngren et al. 1999) and to preferentially activate DA neurons projecting to cortical regions (White and Wang 1983;Goldstein et al. 1993). Accordingly, we postulated that the co-administration of tyrosine and clozapine would potentiate MPFC DA synthesis. We further postulated that if the increased DA synthesis were reflected in increased DA release, then administration of tyrosine to clozapine-pretreated rats would augment MPFC DA levels as measured by in vivo microdialysis. Finally, since haloperidol, but not clozapine, preferentially activates nigrostriatal DA synthesis and release, we anticipated that tyrosine would enhance dialysate DA concentrations in the striatum but not the MPFC of haloperi...

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Section: Discussionmentioning

confidence: 65%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Tyrosine Augments Acute Clozapine- but not Haloperidol-Induced Dopamine Release in the Medial Prefrontal Cortex of the Rat An in vivo Microdialysis Study

Jaskiw

Collins

Pehek

et al. 2001

Neuropsychopharmacology

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“…Linear regression analyses suggest that the association between plasma tyrosine levels and the ability of d-amphetamine to release DA has a steep slope (eg y ¼ À0.34x+19.27: equation for plasma tyrosine vs percent change in [ 11 C]raclopride BP in the t-map). The steepness of slope may be accounted for by the fact that tyrosine hydroxylase is typically 75% saturated with tyrosine (Carlsson and Lindqvist, 1978). The Michaelis-Menten curve suggests that modest decreases in tyrosine availability would have limited effects on the enzyme's hydroxylation rate; below a certain level, though, hydroxylation would be expected to plummet.…”

Section: Discussionmentioning

confidence: 99%

“…Ingestion of the latter mixture induces protein synthesis, leading to a transient reduction in the availability of phenylalanine and tyrosine for entry into the brain. Since the rate-limiting enzyme in catecholamine synthesis, tyrosine hydroxylase, is normally incompletely saturated (Carlsson and Lindqvist, 1978), reduced availability of the AA precursors decreases DA and NE synthesis. On both test days, subjects received a low oral dose of d-amphetamine (0.3 mg/kg, p.o.).…”

Section: Introductionmentioning

confidence: 99%

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

Leyton

Dagher

Boileau

et al. 2003

Neuropsychopharmacol

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Acute phenylalanine/tyrosine depletion (APTD) has been proposed as a new method to decrease catecholamine neurotransmission safely, rapidly, and transiently. Validation studies in animals are encouraging, but direct evidence in human brain is lacking. In the present study, we tested the hypothesis that APTD would reduce stimulated dopamine (DA) release, as assessed by positron emission tomography (PET) and changes in [ 11 C]raclopride binding potential (BP), a measure of DA D2/D3 receptor availability. Eight healthy men received two PET scans, both following d-amphetamine, 0.3 mg/kg, p.o., an oral dose known to decrease [ 11 C]raclopride BP in ventral striatum. On the morning before each scan, subjects ingested, in counter-balanced order, an amino-acid mixture deficient in the catecholamine precursors, phenylalanine, and tyrosine, or a nutritionally balanced mixture. Brain parametric images were generated by calculating [ 11 C]raclopride BP at each voxel. BP values were extracted from the t-map (threshold: t ¼ 4.2, equivalent to po0.05, Bonferroni corrected) and a priori identified regions of interest from each individual's coregistered magnetic resonance images. Both receptor parametric mapping and region of interest analyses indicated that [ 11 C]raclopride binding was significantly different on the two test days in the ventral striatum (peak t ¼ 6.31; x ¼ À25, y ¼ À8, and z ¼ 0.1). In the t-map defined cluster, [ 11 C]raclopride BP values were 11.8 7 11.9% higher during the APTD session (po0.05). The reduction in d-amphetamine-induced DA release exhibited a linear association with the reduction in plasma tyrosine levels (r ¼ À0.82, po0.05). Together, the results provide the first direct evidence that APTD decreases stimulated DA release in human brain. APTD may be a suitable new tool for human neuropsychopharmacology research.

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Carbohydrate craving in obese people: Suppression by treatments affecting serotoninergic transmission

Wurtman

Growdon

et al. 1981

Int. J. Eat. Disord.

159

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We examined the existence of carbohydrate cravings, and the effects on such cravings of treatments that enhance serotonin release, among 24 obese subjects who claimed to have excessive appetites for carbohydrates. Subjects living in a college dormitory for four weeks were given three fixed meals daily and allowed to choose at will among five protein‐rich or five carbohydrate‐rich isocaloric snack foods, provided via a vending machine. For two weeks, they received no treatment (study 1) or a placebo (study 2); for the next two weeks, they received placebo, d‐1 fenfluramine or 1‐tryptophan. All but one of the subjects exhibited a marked preference for carbohydrate‐rich over protein‐rich snacks during the first two weeks of the study. The average daily intake of carbohydrate‐rich snacks was 4.1 ± 0.4 and of protein‐rich snacks 0.8 ± 0.3. Seventeen of the subjects failed to consume any protein snacks on most days during the baseline or test periods, thus it was not possible for us to examine the effect of test treatments on protein snack intake. Fenfluramine administration significantly reduced carbohydrate snacking in six of nine test subjects, as well as in the group as a whole (2.4 ± 0.6 snacks/day vs 4.2 ± 0.6 during the two‐week baseline period). Tryptophan significantly diminished carbohydrate intake in three of the eight treated subjects, and increased it in one subject; it did not significantly modify snacking patterns in the group as a whole. Placebo administration did not affect carbohydrate intake in any of the seven test subjects. These observations show that some obese people do consume carbohydrate‐rich snacks frequently and preferentially, and that this behavior can sometimes be diminished by treatments thought to enhance serotonin's release (fenfluramine) or synthesis (tryptophan).

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Dependence of 5-HT and catecholamine synthesis on concentrations of precursor amino-acids in rat brain

Cited by 315 publications

References 10 publications

Tyrosine Augments Acute Clozapine- but not Haloperidol-Induced Dopamine Release in the Medial Prefrontal Cortex of the Rat An in vivo Microdialysis Study

Tyrosine Augments Acute Clozapine- but not Haloperidol-Induced Dopamine Release in the Medial Prefrontal Cortex of the Rat An in vivo Microdialysis Study

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

Carbohydrate craving in obese people: Suppression by treatments affecting serotoninergic transmission

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