Biochemical aspects of tryptophan depletion in primates

We studied the degree of plasma tryptophan depletion produced by giving normal human males different amounts of a tryptophan-free (T-) amino acid mixture. From the results of this and other studies we concluded that the maximum degree of tryptophan depletion can be produced by a 31.5 g mixture of seven essential amino acids. Administration of a T–amino acid mixture to vervet monkeys lowered tryptophan and 5-hydroxyindoleacetic acid in the cerebrospinal fluid. Levels of tyrosine and the catecholamine metabolites were unchanged. These data support the idea that the effects of T–mixture on mental function in humans which have been reported previously are due to a decrease in 5-hydroxytryptamine.     

急性色氨酸、苯丙氨酸和酪氨酸剥夺对酒依赖者线索暴露诱导的饮酒迫促性的作用

目的:评价急性色氨酸、苯丙氨酸和酪氨酸剥夺(CMD)对酒依赖者线索暴露诱导的饮酒迫促性的作用。方法:采用随机双盲交叉对照的方法,选择符合ICD-10和DSM-Ⅳ诊断标准的男性酒依赖患者12名,并排除任一符合DSM-Ⅳ轴Ⅰ诊断的其他精神障碍。在签署知情同意书的情况下,每位受试者间隔至少7d分别在实验当天禁食的情况下给予含人体必需的16种氨基酸的氨基酸饮料(BLANCE)或缺失色氨酸、苯丙氨酸和酪氨酸的氨基酸饮料(CMD),实验的前一天低蛋白饮食,实验当天结束后给予高蛋白饮食。实验当天,在给予氨基酸饮料前后进行Tiffany饮酒迫促性量表、焦虑可视模拟标尺、抑郁可视模拟标尺、副反应量表测查以及血压、心率检测。给予氨基酸饮料6h后进行非酒精(纯净水)相关线索和酒精(白酒)相关线索暴露,并评价暴露前后饮酒迫促性、焦虑可视模拟标尺分、抑郁可视模拟标尺分和血压、心率的变化。结果:CMD组在非酒精相关线索和酒精相关线索暴露后饮酒意愿(Intention/desire to drinking)和舒张压均增加,差异具有显著性(P=0.0217,0.038),而BLANCE组在非酒精相关线索和酒精相关线索暴露后饮酒意愿、舒张压差异均无显著性。焦虑可视模拟标尺分、抑郁可视模拟标尺分、收缩压、心率在两组中的非酒精相关线索和酒精相关线索暴露前后的差异无显著性。在安全性方面,所有受试者中有1名出现腹泻,但是病人尚能耐受。其余少见的副反应主要有恶心、头晕、困倦等,皆为轻度或中度。结论:急性色氨酸、苯丙氨酸和酪氨酸剥夺(CMD)后酒依赖患者在非酒精和酒精相关线索暴露后的饮酒意愿增加,舒张压增高,但是对焦虑和抑郁情绪没有影响。口服氨基酸饮料的副反应少且轻微。     

Effects on mood of acute phenylalanine/tyrosine depletion in healthy women.

Catecholamines have been implicated in the etiology and pathophysiology of mood and anxiety disorders. In the present study, we investigated the effects of experimentally reducing catecholamine neurotransmission by means of acute phenylalanine/tyrosine depletion (APTD). Healthy female volunteers ingested: (1) a nutritionally balanced amino acid (AA) mixture (n = 14); (2) a mixture deficient in the serotonin precursor, tryptophan (n = 15); or (3) one deficient in the catecholamine precursors, phenylalanine and tyrosine (n = 12). Mood was measured at three times: at baseline and both immediately before and after an aversive psychological challenge (public speaking and mental arithmetic) conducted 5 hours after AA mixture ingestion. Acute tryptophan depletion (ATD) lowered mood and energy and increased irritability scores. These effects were statistically significant only after the psychological challenge. The effect of APTD on mood was similar to that of ATD. APTD did not attenuate the anxiety caused by the psychological challenge. These findings suggest that, in healthy women, reduced serotonin and/or catecholamine neurotransmission increases vulnerability to lowered mood, especially following exposure to aversive psychological events.     

Lack of behavioural effects after acute tyrosine depletion in healthy volunteers

Acute dietary tyrosine depletion has previously been shown to reduce dopamine neurotransmission in both animals and humans. In this study, we investigated the effects of brain dopamine depletion, through acute tyrosine and phenylalanine depletion, on plasma prolactin, mood and neuropsychological function in 12 normal subjects. In a randomized, double-blind, cross-over design, subjects received two amino-acid drinks separated by a week, a nutritionally balanced mixture (Bal) and on the other occasion a tyrosine and phenylalanine deficient mixture (TP-). The plasma ratio of tyrosine and phenylalanine to the other large neutral amino acids decreased significantly on the TP- occasion (-78.7%, p < 0.0001) and there was an increase in plasma prolactin concentration relative to the balanced drink in the seven subjects for whom results were available for both occasions (p < 0.02). Acute tyrosine depletion did not alter mood as measured by visual analogue scale ratings, and measures of memory, attention and behavioural inhibition were also unaffected. Our results are consistent with acute dietary tyrosine depletion causing a reduction in brain dopamine neurotransmission but raise questions about how robust or consistent the effects are on psychological function.     

A dose-finding study on the effects of branch chain amino acids on surrogate markers of brain dopamine function

RATIONALE: We have previously shown in healthy volunteers that an amino acid mixture lacking tyrosine and phenylalanine reduces tyrosine availability to the brain and produces cognitive and neuroendocrine effects consistent with reduced dopamine function. This could provide a potential nutritional approach to disorders such as mania and schizophrenia, which are characterised by overactivity of dopamine pathways. The amino acid mixture we tested previously is unpalatable, whereas mixtures containing only branch chain amino acids can be made more palatable. However, the effects of such mixtures on dopamine function in humans have not been studied. OBJECTIVE: To assess the tolerability of different doses of branch chain amino acids and to measure their effects on neuroendocrine and cognitive measures sensitive to changes in dopamine function. METHODS: We used a randomised, double-blind, cross-over design in 12 healthy volunteers to assess the effect of single oral doses of 10 g, 30 g and 60 g branch chain amino acids on plasma prolactin and a test of spatial recognition memory RESULTS: The branch chain amino acids were well tolerated. The availability of tyrosine for brain catecholamine synthesis decreased in a dose-related manner. As hypothesised, the drink increased both the plasma prolactin and the latency to respond on the spatial recognition memory task. CONCLUSIONS: A drink containing branch chain amino acids is well tolerated in healthy volunteers and produces effects consistent with lowered dopamine function.     

The effects of a branched chain amino acid mixture supplemented with tryptophan on biochemical indices of neurotransmitter function and decision-making

Rationale We have previously shown that a 60-g mixture of branched chain amino acids (BCAAs) lowers the plasma availability of the catecholamine precursors tyrosine (TYR) and phenylalanine (PHE) and produces biochemical and neuropsychological changes consistent with impaired dopamine neurotransmission. However, the BCAA mixture also lowers the ratio of tryptophan (TRP) to BCAA which could impair brain serotonin function.Objectives To determine the biochemical and neuropsychological effects of a BCAA mixture supplemented with TRP.Methods We studied 32 healthy volunteers who were randomly and blindly allocated to either a single administration of amino acid mixture (60 g BCAA and 2 g TRP) or placebo. We carried out venous sampling to measure plasma levels of amino acids and performed selected cognitive tasks sensitive to monoamine manipulation 5 h after mixture ingestion.Results Relative to placebo, the BCAA/TRP mixture substantially lowered the ratio of TYR+PHE:BCAA and increased plasma prolactin. The ratio of TRP:BCAA was also lowered but to a lesser extent. The BCAA/TRP mixture produced significant changes in a task of decision-making where volunteers showed reduced discrimination between gambles with large and small losses.Conclusions A 62 g BCAA/TRP mixture decreases the availability of TYR and PHE for brain catecholamine synthesis and increases plasma prolactin consistent with lowered brain dopamine function. Addition of 2 g TRP to the 60 g BCAA mixture does not prevent a reduction of the ratio TRP:BCAA relative to placebo. The effects of the BCAA/TRP mixture on decision-making suggest a general action of dopamine pathways on the processing of emotional information in risky choice, including punishment-related cues, consistent with suggestions that dopamine mechanisms mediate behavioural responses to aversive as well as appetitive stimuli in instrumental conditioning.     

Attenuation of some subjective effects of amphetamine following tyrosine depletion.

Fifteen healthy volunteers received d-amphetamine (20 mg orally) 2 h after ingesting either a nutritionally balanced amino acid mixture or one lacking the catecholamine precursors, tyrosine and phenylalanine (TYR-free). Plasma tyrosine levels were significantly lowered in subjects who received the TYR-free mixture but mean plasma amphetamine levels were higher. Despite this, the TYR-free mixture appeared to decrease the subjective psychostimulant effects of amphetamine, as determined by visual analogue scales. In contrast, the TYR-free mixture failed to lower the subjective anorectic effect of amphetamine. These findings are consistent with animal experimental studies indicating that tyrosine depletion attenuates the release of dopamine produced by amphetamine but not the release of noradrenaline.     

Effect of a tyrosine-free amino acid mixture on regional brain catecholamine synthesis and release

We report the effects of a tyrosine (and phenylalanine)-free amino acid mixture on tyrosine levels, ex vivo catecholamine synthesis and in vivo catecholamine release in brain regions of the rat. Administration of a tyrosine-free amino acid load reduced tissue levels of tyrosine (−50% after 2 h) in all brain regions examined (frontal cortex, hippocampus, striatum). The tyrosine-free amino acid mixture also reduced DOPA accumulation: this effect was most marked in striatum (−44%) and nucleus accumbens (−34%), areas with a predominantly dopaminergic innervation. Smaller decreases (−20–24%) were detected in other areas (cortex, hippocampus and hypothalamus). The effect on DOPA accumulation was prevented by supplementing the mixture with tyrosine/phenylalanine. The tyrosine-free amino acid mixture did not alter 5-HTP accumulation in any region. In microdialysis experiments, the tyrosine-free amino acid mixture did not consistently alter striatal extracellular dopamine under basal conditions but markedly, and dose-dependently, reduced the release of dopamine induced by amphetamine. In contrast, the tyrosine-free amino acid mixture did not alter either basal or amphetamine-evoked release of noradrenaline in hippocampus. Overall, these studies indicate that administration of a tyrosine-free amino acid mixture to rats depletes brain tyrosine to cause a decrease in regional brain catecholamine synthesis and release. Dopaminergic neurones appear to be more vulnerable to tyrosine depletion than noradrenergic neurones. Received: 19 March 1998 / Final version: 4 June 1998     

Selective effects of acute serotonin and catecholamine depletion on memory in healthy women

There is converging evidence that brain serotonin and dopamine may selectively modulate learning and memory in humans. However, this has not been directly demonstrated. In the current study, we used the method of amino acid precursor depletion to explore the effects of low serotonin and catecholamine function on memory in healthy female volunteers. Participants completed three experimental sessions: (i) tryptophan depletion (TD to lower 5-HT); (ii) tyrosine and phenylalanine depletion (TPD to lower catecholamines); and (iii) a balanced control condition (Bal). All testing was conducted in a double-blind, placebo-controlled, crossover design. Cognitive and mood assessments were performed at baseline and 5 h after ingesting the amino acid mixture. Consistent with previous studies, TD impaired declarative memory consolidation on a structured word-learning task, while TPD, acting to lower brain dopamine availability, impaired spatial working memory. No secondary deficits were observed on measures of attention, short-term memory or subjective mood state. These findings suggest that low brain serotonin versus dopamine selectively impairs memory performance in humans. This may shed light on the role of these neurotransmitters in disorders that are characterized by significant memory impairment.     

Effects of acute combined serotonin and dopamine depletion on cue-induced drinking intention/desire and cognitive function in patients with alcohol dependence

Background

Alcohol cues can precipitate the desire to drink and cause relapse in recovering alcohol-dependent patients. Serotonin and dopamine may play a role in alcohol cue-induced craving. Acute combined tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe) depletion (CMD) in the diet attenuates the synthesis of serotonin and dopamine in the human brain. However, no study of the effects of acute CMD has been previously conducted. Therefore, we investigated whether the attenuation of serotonin and dopamine synthesis changes cue-induced alcohol craving in recently abstinent alcoholics.

Methods

In this double-blind, randomized, placebo-controlled, crossover design, 12 male patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for alcohol dependence were divided into two conditions: (1) monoamine depletion (i.e., consumption of a concentrated amino acid beverage that resulted in a rapid and significant decrease in plasma-free Tyr/Phe/Trp) and (2) balanced condition (i.e., consumption of a similar beverage that contained Tyr/Phe/Trp). The participants were scheduled for two experimental sessions, with an interval of ≥7 days. The cue-induced craving test session was conducted 6 h after each amino acid beverage administration. Drinking urge, blood pressure, heart rate, working memory, and attention/psychomotor performance were assessed before and after administration.

Results

Compared with the balanced condition, the monoamine depletion condition significantly increased drinking intention/desire and diastolic blood pressure. Cognitive performance was not different between the two conditions.

Conclusions

Acute combined serotonin and dopamine depletion may increase drinking intention/desire and diastolic blood pressure without influencing cognitive function.     

The role of dopamine in alcohol self-administration in humans: Individual differences

Objective: To clarify dopamine's role in alcohol self-administration in a heterogeneous sample of drinkers using acute phenylalanine/tyrosine depletion (APTD). Methods: Sixteen men with variable drinking histories were characterized on their ethanol-induced cardiac response, a marker previously proposed to index dopamine system reactivity and vulnerability to alcohol abuse. During separate sessions participants were administered (i) a nutritionally balanced (BAL) amino acid (AA) mixture, (ii) a mixture lacking the dopamine precursors, phenylalanine and tyrosine, and (iii) APTD followed by the dopamine precursor, l-DOPA. Five hours after AA administration, participants could earn units of alcohol using a progressive ratio breakpoint task. Results: Alcohol self-administration was reduced in the APTD and APTD + l-DOPA conditions relative to the BAL condition. In both cases the changes were predicted by ethanol-induced cardiac change. Conclusions: The motivation to drink is likely regulated by more than one neurobiological mechanism. Individual differences in cardiac responsivity to ethanol might provide a peripheral marker of responsiveness to pharmacological manipulations of dopamine.     

Fos immunocytochemical studies on the neuroanatomical sites of action of acute tyrosine depletion in the rat brain

Rationale Acute depletion of brain tyrosine using a tyrosine-free amino acid mixture offers a nutritional approach to reduce central catecholamine function. Recent preclinical data suggest that tyrosine-free amino acid mixtures may have region-specific effects through targeting dopamine neurones.Objectives Here we used fos immunocytochemistry to examine the neuroanatomical sites of action of a tyrosine-free amino acid mixture administered either alone or combined with amphetamine.Methods Rats (male, Sprague Dawley, 240–260 g) were administered (IP) either a tyrosine-free amino acid mixture (1 g/kg), or the same mixture supplemented with tyrosine and phenylalanine (1 g/kg). Mixtures were injected twice (1 h apart) followed 1 h later by amphetamine (2 mg/kg SC). Two hours later, cardiac perfusion was performed and brains were processed for fos immunocytochemistry. Fos positive cells were counted using computer imaging software.Results The tyrosine-free amino acid mixture alone did not alter fos expression in ten regions of the rat forebrain compared to saline controls. However, the mixture reduced the increase in fos expression evoked by amphetamine. This effect was region-specific and was greatest in caudate putamen, nucleus accumbens, bed nucleus stria terminalis and lateral habenula, and lacking in other areas including cingulate and insular cortices, lateral septum and central amygdaloid nucleus. Moreover, in most regions the effect of the tyrosine-free mixture was less after tyrosine and phenylalanine supplementation.Conclusions In summary, a tyrosine-free amino acid mixture reduced amphetamine-induced fos expression but this effect was region-specific and included dopamine-rich regions. These data further support the idea that tyrosine depletion strategies have potential as treatments for mania and other hyperdopaminergic states.     

Differential effects of acute serotonin and dopamine depletion on prepulse inhibition and p50 suppression measures of sensorimotor and sensory gating in humans.

Schizophrenia is associated with impairments of sensorimotor and sensory gating as measured by prepulse inhibition (PPI) of the acoustic startle response and P50 suppression of the auditory event-related potential respectively. While serotonin and dopamine play an important role in the pathophysiology and treatment of schizophrenia, their role in modulating PPI and P50 suppression in humans is yet to be fully clarified. To further explore the role of serotonin and dopamine in PPI and P50 suppression, we examined the effects of acute tryptophan depletion (to decrease serotonin) and acute tyrosine/phenylalanine depletion (to decrease dopamine) on PPI and P50 suppression in healthy human participants. In addition, we also examined for the first time, the effects of simultaneous serotonin and dopamine depletion (ie combined monoamine depletion) on PPI and P50 suppression. The study was a double-blind, placebo-controlled cross-over design in which 16 healthy male participants completed the PPI and P50 paradigms under four acute treatment conditions: (a) balanced/placebo control, (b) acute tryptophan depletion, (c) acute tyrosine/phenylalanine depletion, and (d) acute tyrosine/phenylalanine/tryptophan depletion (combined monoamine depletion). Selective depletion of dopamine had no significant effect on either PPI or P50 suppression, whereas selective serotonin depletion significantly disrupted PPI, but not P50 suppression. Finally, the simultaneous depletion of both serotonin and dopamine resulted in significant reduction of both PPI and P50 suppression. We suggest these results can be explained by theories relating to optimal levels of monoaminergic neurotransmission and synergistic interactions between serotonergic and dopaminergic systems for normal 'gating' function. These findings suggest that a dysfunction in both serotonin and dopamine neurotransmission may, in part, be responsible for the gating deficits observed in schizophrenia, and their normalization following administration of atypical antipsychotic drugs.     

Tyrosine depletion attenuates dopamine function in healthy volunteers

RATIONALE: Tyrosine depletion has been shown to reduce dopamine over activity in animal and human investigations. However, the effects on basal dopamine function have not been explored. Such information could establish tyrosine depletion as an effective probe of dopamine function in healthy volunteers and would also have relevance for future therapeutic applications of this manipulation. OBJECTIVE: The present study investigated the effect of acute tyrosine depletion on dopamine function in healthy volunteers using a combination of neuroendocrine, neuropsychological and subjective measures. METHODS: On one occasion, volunteers received an amino acid drink selectively lacking tyrosine and phenylalanine (TYR-free), whilst on the other they received a balanced (BAL) amino acid drink. Plasma prolactin, amino acid levels and subjective state were monitored over 6 h following the two drinks, and volunteers also completed a battery of tests from the CANTAB, including measures of spatial memory previously found to be sensitive to changes in dopamine function. RESULTS: Plasma prolactin levels rose following the TYR-free drink relative to the balanced mixture, indicative of decreased dopamine neurotransmission within the hypothalamus. Following the TYR-free drink, volunteers were impaired at spatial recognition memory and spatial working memory. Volunteers also tended to report that they felt less good following the TYR-free than the BAL mixture. CONCLUSION: Tyrosine depletion in healthy volunteers affected baseline dopamine function on the different measures employed in this study. Tyrosine depletion would thereby seem valuable as a probe of dopamine function in human volunteers. Ratings of depression and other aspects of cognitive function were unaffected, suggesting that this manipulation may be free of significant side effects when used as a treatment for conditions characterised by dopamine over activity, such as acute mania and schizophrenia.     

Effects of chronic fenfluramine on blood serotonin,cerebrospinal fluid metabolites,and behavior in monkeys

The effects of long term (70 days) fenfluramine treatment on selected physiological and behavioral measures were examined in four adult male vervet monkeys (Cercopithecus aethiops sabaeus). Relative to pretreatment baseline values, whole blood serotonin (WBS) and cerebrospinal fluid 5-hydroxyindole acetic acid (5-HIAA) were reduced, cerebrospinal fluid homovanillic acid (HVA) was unaltered, and aggressive and locomotor behavior were increased. Both physiological and behavioral effects were reversible: all measures returned to baseline values in the 35 day post-treatment period, with WBS resuming pretreatment values more rapidly than CSF 5-HIAA. At the relatively low doses (1–4 mg/kg/day) employed in the present study fenfluramine produced behavioral effects similar to those resulting from PCPA and opposite to those following tryptophan administration. Thus the behavioral effects of long-term fenfluramine may involve reductions in serotonergic transmission.     

The subjective and cognitive effects of acute phenylalanine and tyrosine depletion in patients recovered from depression.

Although there is evidence for the involvement of dopamine (DA) in unipolar depression, no published study has yet used the technique of acute phenylalanine and tyrosine depletion (APTD), a dietary intervention that selectively lowers DA synthesis, in order to investigate the role of DA in mood disturbance. Tyrosine and phenylalanine depleted and placebo amino acid drinks were administered to 20 patients recovered from depression in a double-blind, placebo-controlled, crossover design. Measures included subjective effects, Hamilton Depression Rating Scale scores, and a comprehensive battery of well-validated computerized cognitive tests. APTD induced a substantial reduction in the ratio of plasma tyrosine and phenylalanine to large neutral amino acids. However, relapse of depressive symptoms was not seen. Although performance on most cognitive tests was unaffected, there was a selective effect on decision-making, with APTD causing participants to bet significantly less. In conclusion, These results suggest a specific role for the involvement of DA in reward/punishment processing in humans. While APTD did not induce relapse in any participant, it did cause patients recovered from depression to show lowered sensitivity to reward in a gambling game. It is hypothesized that tests involving reward/punishment processing are preferentially affected by DA depletion, and that a more complete account of depression is likely to result from considering the roles played by serotonin, noradrenaline, and DA in mediating the various cognitive and clinical symptoms, including anhedonia.     

Effect of acute tyrosine depletion in using a branched chain amino-acid mixture on dopamine neurotransmission in the rat brain.

Central dopamine function is reduced by decreasing the availability of the catecholamine precursor, tyrosine, using a tyrosine-free amino acid mixture containing multiple large neutral as well as branched chain amino-acids, which compete with tyrosine for uptake into the brain. Current mixtures are cumbersome to make and administer, and unpalatable to patients and volunteers. Here, we investigate whether individual or limited amino-acid combinations could reduce brain tyrosine levels and hence dopamine function. Measurements of regional brain tyrosine levels, catecholamine and indoleamine synthesis (L-DOPA and 5-HTP accumulation, respectively) were used to identify an effective paradigm to test in neurochemical, behavioral and fos immunocytochemical models. Administration of leucine or isoleucine, or a mixture of leucine, isoleucine, and valine reduced tyrosine and 5-HTP, but not L-DOPA accumulation. A mixture of leucine, valine, and isoleucine supplemented with tryptophan reduced brain tyrosine and L-DOPA, but not 5-HTP. In microdialysis experiments this amino-acid mixture reduced basal and amphetamine-evoked striatal dopamine release, as well as amphetamine-induced hyperactivity. This mixture also reduced amphetamine-induced fos expression in striatal areas. In conclusion, the present study identified a small combination of amino acids that reduces brain tyrosine and dopamine function in a manner similar to mixtures of multiple amino acids. This minimal mixture may have use as a dopamine reducing paradigm in patient and volunteer studies.     

Comparison of the effects of alpha-methyl-p-tyrosine and a tyrosine-free amino acid load on extracellular noradrenaline in the rat hippocampus in vivo

Peripheral administration of an amino acid load lacking tyrosine and its precursor, phenylalanine, causes a lowering of central tyrosine levels. The aim of the present study was to examine the effects of tyrosine depletion on extracellular noradrenaline using microdialysis. Extracellular noradrenaline was measured in hippocampus of the anaesthetized rat under both baseline conditions (with reuptake inhibitor, desipramine, in the perfusion medium) and following administration of the alpha2-adrenoreceptor antagonist, idazoxan. The tyrosine free amino acid load did not alter either baseline noradrenaline or the twofold rise in noradrenaline evoked by idazoxan compared with saline controls. In contrast, the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine, caused a marked reduction in baseline extracellular noradrenaline and abolished the rise induced by idazoxan. In conclusion, the present data indicate that under the conditions used, a tyrosine-free amino acid mixture may not be an effective means to interfere with central noradrenaline function. This contrasts with recent findings demonstrating that the tyrosine-depletion approach can be used to decrease presynaptic dopamine function.     

The effect of raising or lowering tryptophan levels on aggression in vervet monkeys

Social groups of vervet monkeys (Cercopithecus aethiops) were given amino acid mixtures that were tryptophan-free (T-), nutritionally balanced (B), or contained excess tryptophan (T+). The T- mixture caused a marked decrease in plasma tryptophan and the T+ mixture a large increase. Behavioral observations were made on the animals after administration of the amino acid mixtures both during spontaneous activity and while the (fasted) animals were competing for food newly placed in the feeder. The only effect of the biochemical manipulations on spontaneous aggression was an increase in aggression of the male animals with the T- mixture. During competition for the food the T- mixture increased and the T+ mixture decreased aggression in the males, while the T+ mixture decreased aggression in females. These data indicate that brain 5-hydroxytryptamine can influence aggression in a primate and suggest that altered tryptophan levels can influence aggression more reliably at higher levels of arousal.     

Acute serotonin and dopamine depletion improves attentional control: findings from the stroop task.

Schizophrenia is associated with impairments of attentional control on classic experimental paradigms such as the Stroop task. However, at a basic level the neurochemical mechanisms that may be responsible for such impairments are poorly understood. In this study, we sought to investigate the influence of brain monoamine function on Stroop task performance in healthy participants using the established methods of acute dietary serotonin, dopamine, and combined monoamine depletion. The study was a double-blind placebo controlled design in which 12 healthy male participants completed the Stroop task under four acute treatment conditions: (a) balanced/placebo control, (b) acute tryptophan depletion, (c) acute tyrosine/phenylalanine depletion, and (d) acute tyrosine/phenylalanine/tryptophan depletion (combined monoamine depletion). Decreased Stroop interference indicating improved attentional control was observed after both tryptophan depletion and tyrosine/phenylalanine depletion, while there was no significant change in interference after combined monoamine depletion. Findings suggest that reduced tonic dopamine or serotonin activity within specific neural circuits (such as the striatum, anterior cingulate, or prefrontal cortex) may play a critical role in attentional control, possibly by improving gating of information via reducing noise in monoaminergic systems. These findings enhance our understanding of the neurochemical basis of attentional control and the possible cause of attentional control deficits in schizophrenia.