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

Abstract

Dopamine (DA) neurotransmission is critical for motivational processing. We assessed whether disruption of DA synthesis in healthy controls using an amino-acid beverage devoid of catecholamine precursors (tyrosine-phenylalanine depletion (TPD)) would blunt recruitment of the nucleus accumbens (NAcc) by rewards. Sixteen controls ingested each of a tyr/phe-depleting beverage (DEP) or a tyr/ phe-balanced (BAL) control beverage in two laboratory visits. Five hours after consumption of each drink, subjects underwent functional magnetic resonance imaging while they viewed anticipatory cues to respond to a target to either win money or avoid losing money. TPD did not exert main effects on mood or on task behavior, but affected brain activation. In right NAcc, TPD blunted activation by anticipation of high rewards. In left NAcc, recruitment anticipating high rewards was modulated by individual differences in mood change across the DEP drink day, where subjects whose mood worsened following TPD (relative to within-day mood change under BAL conditions) also showed lower activation under DEP conditions relative to BAL conditions. Exploratory analysis indicated that TPD qualitatively blunted the voxel-wise spatial extent of suprathreshold activation by reward anticipation. Finally, loss outcomes activated anterior insula under DEP conditions but not under BAL conditions. These data indicate that: (1) dietary depletion of catacholamine precursors will blunt dopaminergic mesolimbic activity, and (2) in controls, synthetic pathways of this neurocircuitry maintain sufficient buffering capacity to resist an effect on motivated behavior. Additional studies are needed to determine if clinical populations would show similar resistance to behavioral effects of TPD.

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“…122 Dietary depletion of DA precursors, which reduces DA synthesis 123 , attenuates participants' sensitivity to rewards during decision-making 124 and also increases punishment learning relative to reward learning 125 , with some reporting corresponding reductions in reward-elicited BOLD responses in the striatum. 126 Research using DA receptor antagonists to block transmission has yielded less consistent results, possibly owing to doses used and the actions of these compounds on other monoamine systems as well as inhibitory autoreceptors. 122 L-DOPA (which increases DA synthesis), amphetamine and methylphenidate (which block DA reuptake) and D2/3 receptor agonists generally increase a variety of the processes depicted in Fig 1, including: speed 127 and vigour 128 of responses (action); effortful 61 and risky 129 choices (cost-benefit decision making); reward learning; 130 and associated reward-related striatal BOLD responses (reviewed in ref 109).…”