6: J Psychiatr Res 1982-83;17(2):175-80 Tyrosine for depression. Gelenberg AJ, Wojcik JD, Gibson CJ, Wurtman RJ. The catecholamine hypothesis of affective disorders postulates that depression reflects inadequate norepinephrine activity at unspecified brain centers that regulate mood. In light of experimental data showing that the oral administration of tyrosine, precursor of the catecholamine series of neurotransmitters, can increase brain norepinephrine concentrations and activity, we have conducted preliminary trials of tyrosine in depressed outpatients. Initial results are encouraging, and we are now conducting a double-blind, parallel-group trial comparing tyrosine to the tricyclic antidepressant imipramine and to placebo in non-bipolar outpatients with major depression. Publication Types: Review PMID: 6764934 [PubMed - indexed for MEDLINE]
5: Life Sci 1984 Jun 4;34(23):2225-31 Tyrosine prevents behavioral and neurochemical correlates of an acute stress in rats. Reinstein DK, Lehnert H, Scott NA, Wurtman RJ. Exposure of rats to an acute, uncontrollable stressor can increase brain norepinephrine (NE) turnover and decrease locomotor and exploratory behavior. We examined the ability of exogenous tyrosine, NE's amino acid precursor, to protect rats from developing these neurochemical and behavioral changes when stressed. Animals pretreated with saline or tyrosine (200 mg/kg, i.p.) were subjected to tail shock (15 v, 2 mA, 5 sec/30 sec) or to no shock during a 60-min period. Exposure to shock depleted NE and increased its turnover [as indicated by altered NE and 3-methoxy-4-hydroxy-phenylene-glycol sulfate levels (MHPG-SO4)] within the locus coeruleus, the hippocampus and the hypothalamus. Behavioral deficits were observed using measures of locomotion, standing on hind legs, and hole-poking in an open-field apparatus. Animals given tyrosine before shock displayed neither shock-induced NE depletion nor the deficits in locomotion and hole-poking; brain MHPG-SO4 levels tended to be greater than after shock alone. These observations suggest that the stress caused NE to be released from some neurons more rapidly than it could be restored by synthesis or reuptake, thereby impairing noradrenergic transmission and NE-dependent exploratory behaviors. Tyrosine administration presumably enhanced the transmitter's synthesis in stressed animals, thereby preventing both the neurochemical and the behavioral deficits. PMID: 6727560 [PubMed - indexed for MEDLINE]
1: Brain Res Bull 1989 Apr;22(4):759-62 Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Banderet LE, Lieberman HR. U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760-5007. Acutely stressful situations can disrupt behavior and deplete brain norepinephrine and dopamine, catecholaminergic neurotransmitters. In animals, administration of tyrosine, a food constituent and precursor of the catecholamines, reduces these behavioral and neurochemical deficits. Using a double-blind, placebo-controlled crossover design we investigated whether tyrosine (100 mg/kg) would protect humans from some of the adverse consequences of a 4.5 hour exposure to cold and hypoxia. Tyrosine significantly decreased symptoms, adverse moods, and performance impairments in subjects who exhibited average or greater responses to these environmental conditions. These results suggest that tyrosine should be evaluated in a variety of acutely stressful situations. Publication Types: Clinical trial Controlled clinical trial PMID: 2736402 [PubMed - indexed for MEDLINE]
7: Life Sci 1985 Dec 9;37(23):2157-63 Dietary tyrosine suppresses the rise in plasma corticosterone following acute stress in rats. Reinstein DK, Lehnert H, Wurtman RJ. Acute, uncontrollable stress increases norepinephrine (NE) turnover in the rat's brain (depleting NE) and diminishes the animal's subsequent tendency to explore a novel environment. Pre-treatment with tyrosine can reverse these adverse effects of stress, presumably by preventing the depletion of NE in the hypothalamus. Numerous studies suggest that NE inhibits the release of adrenocorticotropic hormone (ACTH) by suppressing corticotropic releasing factor (CRF) secretion in the hypothalamus. In the present study, we found that pre-treatment with supplemental tyrosine not only prevented the behavioral depression and hypothalamic NE depletion observed after an acute stress, but also suppressed the rise in plasma corticosterone. These results support a role for brain NE in stress-induced corticosterone secretion and demonstrate that supplemental tyrosine can protect against several adverse consequences of such stress. PMID: 4068899 [PubMed - indexed for MEDLINE]
4: Psychoneuroendocrinology 2001 Apr;26(3):307-17 Enhanced memory for emotional material following stress-level cortisol treatment in humans. Buchanan TW, Lovallo WR. Veterans Affairs Medical Center and Department of Psychiatry and Behavioral Sciences Labs (151A), University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Memory tends to be better for emotionally arousing information than for neutral information. Evidence from animal studies indicates that corticosteroids may be necessary for this memory enhancement to occur. We extend these findings to human memory performance. Following administration of cortisol (20 mg) or placebo, participants were exposed to pictures varying in emotional arousal. Incidental memory for the pictures was assessed one week later. We show that elevated cortisol levels during memory encoding enhances the long-term recall performance of emotionally arousing pictures relative to neutral pictures. These results extend previous work on corticosteroid enhancement of memory and suggest that high cortisol levels during arousing events result in enhanced memory in humans. Publication Types: Clinical trial Randomized controlled trial PMID: 11166493 [PubMed - indexed for MEDLINE]
8: Brain Res Bull 1994;33(3):319-23 Effect of tyrosine on cognitive function and blood pressure under stress. Deijen JB, Orlebeke JF. Department of Psychophysiology, Vrije Universiteit, Amsterdam, The Netherlands. The effects of tyrosine on mood, performance, heart rate and blood pressure of 16 healthy young subjects were assessed. Subjects were tested on two separate days, one test session after ingestion of 100 mg/kg tyrosine and the other test session after placebo, in random order. While performing a number of stress sensitive tasks, subjects were exposed to a stressor consisting of 90 dB noise. Tyrosine was found to improve the performance on two cognitive tasks, which were performed 1 h after administration of the medication and which could be characterized as highly sensitive to stress. In addition, tyrosine decreased diastolic blood pressure 15 min after ingestion, while 1 h after ingestion diastolic blood pressure was the same with tyrosine and placebo. No effects on mood, systolic blood pressure and heart rate were found. Publication Types: Clinical trial Randomized controlled trial PMID: 8293316 [PubMed - indexed for MEDLINE]
2: Aviat Space Environ Med 1995 Apr;66(4):313-9 The effects of tyrosine on cognitive performance during extended wakefulness. Neri DF, Wiegmann D, Stanny RR, Shappell SA, McCardie A, McKay DL. Naval Aerospace Medical Research Laboratory, Pensacola, FL, USA. Tyrosine, a large neutral amino acid found in dietary proteins, has received recent attention as a potential treatment for stress. The behavioral effects of tyrosine were examined during an episode of continuous nighttime work involving one night's sleep loss. Subjects performed nine iterations of a battery of performance tasks and mood scales for approximately 13 h, beginning at 1930 and ending at 0820. They remained awake throughout the day on which the experiment began and were awake for more than 24 h by the end of testing. Six hours after the experiment began, one-half of the subjects received 150 mg.kg-1 tyrosine in a split dose while the other half received cornstarch placebo in a double-blind procedure. Tyrosine administration was associated with a significant amelioration of the usual performance decline on a psychomotor task and a significant reduction in lapse probability on a high-event-rate vigilance task. The improvements lasted on the order of 3 h. The results of this study also suggest that tyrosine is a relatively benign treatment at this dose. After further testing with other doses and timing of administration, tyrosine may prove useful in counteracting performance decrements during episodes of sustained work coupled with sleep loss. Publication Types: Clinical trial Randomized controlled trial PMID: 7794222 [PubMed - indexed for MEDLINE]
3: Aviat Space Environ Med 1992 May;63(5):364-9 Tyrosine and its potential use as a countermeasure to performance decrement in military sustained operations. Owasoyo JO, Neri DF, Lamberth JG. Naval Aerospace Medical Research Laboratory, Pensacola, FL. We review the biochemistry and physiological role of the amino acid tyrosine in normal and stressful situations such as military sustained operations. Sustained operations consist of continuous work periods exceeding 12 h and often involve sleep loss and fatigue. These, in turn, can lead to stress, anxiety, mood deterioration, and performance decrement. Experimental data in the literature suggest that tyrosine, a precursor of the neurotransmitter norepinephrine, may be useful in counteracting any stress-related performance decrement and mood deterioration in the following way. First, various forms of stress induce brain depletion of catecholamines, especially norepinephrine, in animals. Second, brain norepinephrine levels are closely related to stress-induced performance decrement in animals. Third, the administration of tyrosine may minimize or reverse stress-induced performance decrement by increasing depleted brain norepinephrine levels. The types of performance degradation expected in military sustained operations and the potential physiological role tyrosine might play in improving mood and performance are discussed. Publication Types: Review Review, tutorial PMID: 1599383 [PubMed - indexed for MEDLINE]
9: Clin Neuropharmacol 1994 Feb;17(1):53-62 L-tyrosine pharmacotherapy of schizophrenia: preliminary data. Deutsch SI, Rosse RB, Schwartz BL, Banay-Schwartz M, McCarthy MF, Johri SK. Department of Veterans Affairs Medical Center, Psychiatry Service, Washington, DC 20422. The utility of L-tyrosine (10 g/day in four divided doses) as an adjuvant to molindone (150 mg/day) in the treatment of schizophrenia was investigated using a placebo-controlled, double-blind crossover design (3 weeks on L-tyrosine, 3 weeks on placebo). The objective of this inpatient study was to increase dopaminergic neural transmission along mesocortical projections in patients by increasing the precursor availability of L-tyrosine for dopamine biosynthesis. Theoretically, this approach might lessen both negative and positive symptoms of schizophrenia and improve frontal lobe-mediated neuropsychological performance. There was no evidence of statistically significant improvement conferred by L-tyrosine as measured by weekly Brief Psychiatric Rating Scale (BPRS), Schedule for the Assessment of Negative Symptoms (SANS), or Clinical Global Impressions (CGI) scales. The 12-h trough plasma level of L-tyrosine was significantly higher in all patients during the L-tyrosine phase of the study (t = -3.9, df = 20, p = 0.0009). At the end of each 3-week study period, no significant differences could be found in Wisconsin Card Sorting Test (WCST) or memory test performance. Smooth-pursuit eye movement (SPEM) performance had significantly more saccadic intrusions during the L-tyrosine supplementation phase compared to the placebo period. This increase in saccades during SPEM suggests that the tyrosine supplementation might have had some central effect. Publication Types: Clinical trial Randomized controlled trial PMID: 8149360 [PubMed - indexed for MEDLINE]
1: Mil Med 1989 Mar;154(3):144-6 Dietary tyrosine as an aid to stress resistance among troops. Salter CA. In past conflicts battle stress casualties have caused a serious exit of troops from the frontlines. Recent research has linked stress-caused impairments of performance with depletion of brain stores of the neurotransmitter norepinephrine (NE), which functions in neural tracts responding to stress. The amino acid tyrosine (TYR) is the dietary precursor for NE, and supplementation with TYR has been demonstrated in the laboratory to alleviate declines in both neural NE and performance during stress. Thus, TYR supplementation might help to prevent and treat stress casualties in combat. Further research is called for to verify this hypothesis. PMID: 2496341 [PubMed - indexed for MEDLINE]
1: Physiol Behav 2001 Feb;72(3):311-6 Tyrosine improves behavioral and neurochemical deficits caused by cold exposure. Yeghiayan SK, Luo S, Shukitt-Hale B, Lieberman HR. Military Nutrition and Biochemistry Division, United States Army Research Institute of Environmental Medicine, Kansas Street, Natick, MA 01760-5007, USA. sylva.yeghiayan@na.amedd.army.mil The effects of acute cold stress were assessed behaviorally and neurochemically. The norepinephrine (NE) precursor, tyrosine (TYR), the catecholamine-releasing compound, amphetamine (AMPH), and the adrenoceptor agonist, phenylpropanolamine (PPA), were administered systemically either alone or in conjunction with TYR 30 min prior to cold exposure. All three sympathomimetic treatments dose-dependently improved performance in a forced swim test following hypothermia (T(c)=30 degrees C). AMPH/TYR or PPA/TYR combinations further improved performance vs. either agent given alone. Microdialysis showed elevated hippocampal NE concentrations in response to hypothermia. TYR further elevated NE concentration in cold/restrained rats vs. saline (SAL)-treated controls. These results suggest that sympathomimetic agents, including the nutrient TYR, which enhance noradrenergic function, improve performance in animals acutely stressed by hypothermia. PMID: 11274672 [PubMed - indexed for MEDLINE]
12: Physiol Behav 1996 Apr-May;59(4-5):867-71 Tyrosine administration prevents hypoxia-induced decrements in learning and memory. Shukitt-Hale B, Stillman MJ, Lieberman HR. GEO-CENTERS, INC., Newton Centre, MA 02159, USA. Exposure to hypobaric hypoxia rapidly produces decrements in learning and memory. Tyrosine, a neurotransmitter precursor, has beneficial behavioral effects when administered to animals and humans exposed to various acute stressors. To determine whether tyrosine would protect rats from the adverse effects of hypobaric hypoxia on spatial reference and working memory, it was administered to 27 male Fischer 344 rats tested in the Morris water maze. Rats were tested starting at 2 and 6 h of an 8 h exposure to a simulated altitude of 5950 m (19,500 ft) or sea level. Tyrosine or placebo was administered 1/2 h prior to each testing session (400 mg/kg, IP). Altitude exposure significantly increased working memory escape latency; treatment with tyrosine reversed this decrement. There was no effect of altitude or tyrosine on reference memory. There were also no treatment-related differences in performance when animals were tested the next day at sea level. The beneficial effects of tyrosine on working memory performance may be due to a direct effect of tyrosine on memory, alleviation of a hypoxia-induced retardation of learning, or to other central or peripheral effects of this dietary catecholamine precursor. PMID: 8778879 [PubMed - indexed for MEDLINE]