Fear expression is suppressed by tyrosine administration

Alessandro Soranzo,Luca Aquili

doi:10.1038/s41598-019-52610-x

Abstract

Animal studies have demonstrated that catecholamines regulate several aspects of fear conditioning. In humans, however, pharmacological manipulations of the catecholaminergic system have been scarce, and their primary focus has been to interfering with catecholaminergic activity after fear acquisition or expression had taken place, using L-Dopa, primarily, as catecholaminergic precursor. Here, we sought to determine if putative increases in presynaptic dopamine and norepinephrine by tyrosine administered before conditioning could affect fear expression. Electrodermal activity (EDA) of 46 healthy participants (24 placebo, 22 tyrosine) was measured in an instructed fear task. Results showed that tyrosine abolished fear expression compared to placebo. Importantly, tyrosine did not affect EDA responses to the aversive stimulus (UCS) or alter participants’ mood. Therefore, the effect of tyrosine on fear expression cannot be attributed to these factors. Taken together, these findings provide evidence that the catecholaminergic system influences fear expression in humans.

Highlights

Animal studies have demonstrated that catecholamines regulate several aspects of fear conditioning
The task had a fear expression phase during which a conditioned stimulus (CS+) predicted the occurrence of an unconditioned stimulus (UCS: 75 db loud beep played through a pair of earphones) whereas another conditioned stimulus predicted the occurrence of a neutral event (CS−, which was a fixation dot, Fig. 3A)
Numerous studies over the last decade have demonstrated an involvement of dopamine and norepinephrine in both fear acquisition, expression and extinction

Summary

Introduction

Animal studies have demonstrated that catecholamines regulate several aspects of fear conditioning. The effect of tyrosine on fear expression cannot be attributed to these factors Taken together, these findings provide evidence that the catecholaminergic system influences fear expression in humans. The term fear expression is used to describe conditioned responses (CR) that have developed following fear acquisition when the CS is presented in the absence of the UCS. Animal studies have demonstrated the involvement of dopaminergic D1, D2, D3 and D4 receptors in the amygdala in fear conditioning. Animal studies have revealed an important role of norepinephrine (NE) in fear conditioning (for an extensive review, please see[14]). Despite some complex interaction effects, there is robust evidence to suggest that dopamine and norepinephrine are involved in the acquisition/expression of fear responses

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Conclusion