An amino acid mixture deficient in phenylalanine and tyrosine reduces cerebrospinal fluid catecholamine metabolites and alcohol consumption in vervet monkeys

Abstract

An amino acid mixture devoid of tryptophan, given orally, was previously shown to reduce cerebrospinal fluid levels of tryptophan and 5-hydroxyindoleacetic acid in vervet monkeys, as compared to a control mixture containing all essential amino acids. In the present study, we tested the possibility that a similar amino acid mixture containing tryptophan, but devoid of phenylalanine and tyrosine (the amino acid precursors of catecholamine neurotransmitters), would influence dopamine and noradrenaline metabolism. Five hours after the administration of this mixture to vervet monkeys, cerebrospinal fluid levels of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol were reduced by 27.4% and 26.9%, respectively. Both effects were statistically significant. Plasma tyrosine (-30%) and the ratio of tyrosine to the sum of other large neutral amino acids (sigmaLNAA) were also significantly reduced. The behavioral efficacy of phenylalanine/tyrosine depletion was compared with that of tryptophan depletion in a primate model of voluntary alcohol consumption. All three drinks lowered alcohol consumption, but the effects of the tryptophan-deficient amino acid mixture were not different from those of the balanced amino acid control. The phenylalanine/tyrosine-deficient drink differentially lowered alcohol consumption, consistent with other data in this species and elsewhere implicating dopamine in the rewarding effects of alcohol.

Acute Serotonin and Dopamine Depletion Improves Attentional Control: Findings from the Stroop Task

“…These depletion levels were similar in magnitude to those observed in previous studies using the TYR/PHE depletion method (plasma TYR/PHE: 53-76% depletion; TYR/PHE to LNAA ratio: 99% depletion) (Leyton et al, 1999(Leyton et al, , 2000Harmer et al, 2001). Previous studies in animals with TYR depletion between 30 and 40%, have shown significant reductions in catecholamine metabolites (Palmour et al, 1998) and catecholamine synthesis in the brain (Jaskiw and Bongiovanni, 2004;McTavish et al, 1999a). In humans, depletion of TYR/PHE to this magnitude has been shown to cause significant increases in plasma prolactin levels (an indirect measure of dopamine function) (Harmer et al, 2001;Harrison et al, 2004) and to impair dopamine dependent cognitive processes such as spatial working memory function (Harmer et al, 2001) due to reductions in 'tonic' dopamine.…”

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

“…These depletion levels are equivalent to those observed using ATPD in previous studies (Harmer et al, 2001;Leyton et al, 2000). Furthermore, APTD studies with depletion levels of this magnitude have noted significant reductions in catecholamine metabolites (Palmour et al, 1998) and catecholamine synthesis (Jaskiw and Bongiovanni, 2004;McTavish et al, 1999a, b), and significant increases in plasma prolactin levels (an indirect measure of dopamine function) (Harmer et al, 2001). However, depletion of dopamine with ATPD in the present study resulted in no significant change in either PPI or P50 suppression.…”

Dietary Tyrosine/Phenylalanine Depletion Effects on Behavioral and Brain Signatures of Human Motivational Processing

“…Second, although scans were scheduled at the nadir of plasma TyrPhe/LNAA ratio, when plasma prolactin concentrations (as a peripheral marker of reduced central DA function) previously elicited by this mixture were at their peak (Harmer et al, 2001), it is possible that the nadir of restricted central catecholamine synthesis occurred later (Palmour et al, 1998). Moreover, TPD decreases norepinephrine (NE) synthesis as well as DA synthesis (eg, Palmour et al, 1998). Therefore, activation changes cannot be definitively attributed to changes in DA synthesis.…”

“…Large neutral amino acids (LNAAs) compete with Tyr for CNS uptake (Oldendorf, 1973) and stimulate hepatic protein synthesis to incorporate extant Tyr into proteins (Harper et al, 1970). This markedly lowers concentrations of Tyr in the plasma (Moja et al, 1996;Palmour et al, 1998) as well as catecholamine metabolites in the CSF (Palmour et al, 1998) and striatum (Biggio et al, 1976) within hours. Perturbations of Tyr/Phe availability have altered responses to DA-mediated pharmacological or environmental challenges (reviewed in Milner and Wurtman, 1986;Tam and Roth, 1997).…”