Tyrosine enhances behavioral and mesocorticolimbic dopaminergic responses to aversive conditioning.
Tyrosine is a precursor in the biosynthesis of catecholamines and, when administered systemically, has been shown to enhance the in vivo rate of tyrosine hydroxylation in the medial prefrontal cortex. Additionally, exogenous tyrosine has been demonstrated to enhance the pharmacologically-induced increase in dopamine metabolism seen following administration of haloperidol or the anxiogenic B-carboline, FG-7142. In this report, we examine the effect of a physiologically relevant dose of tyrosine (25 mg/kg) on biochemical and behavioral consequences of aversive conditioning. Rats were conditioned to fear a tone by pairing it with footshock, so that when challenged with the tone alone, rats responded with immobility, defecation, and elevated dopamine metabolism in the medial prefrontal cortex and nucleus accumbens. When tyrosine was administered on the test day (tones alone), the rats displayed an even greater elevation of dopamine metabolism in the nucleus accumbens and prolonged immobility to the tone, compared to the saline/conditioned controls. Tyrosine did not alter mobility or dopamine utilization in the nucleus accumbens in nonconditioned controls. However, dopamine metabolism in the medial prefrontal cortex of nonconditioned rats treated with tyrosine was increased to levels similar to those in the conditioned groups. This may be accounted for by handling and by exposure to an unfamiliar environment necessary for nonconditioned controls. We conclude that exogenous tyrosine is able to 1) elevate stress-induced dopamine metabolism in the nucleus accumbens, 2) alter dopamine utilization in the medial prefrontal cortex of handled, nonconditioned controls, and 3) enhance fear-induced immobilization. These data suggest a role for dietary tyrosine in biochemical and behavioral responses to aversive stimuli.
Morrow
B A
BA
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA.
Elsworth
J D
JD
Roth
R H
RH
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003213:Conditioning, Psychological; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000494:pharmacology*
D015102:3,4-Dihydroxyphenylacetic Acid; D014443:Tyrosine; D004298:Dopamine