Region-specific effects of a Trosine-Free amino acid mixture on amphetamine-induced changes in BOLD fMRI signal in the rat brain

Background: Acute depletion of tyrosine using a tyrosine-free amino acid mixture offers a novel dietary approach to inhibit activated dopamine pathways in the brain. This study investigated the potential of in vivo functional magnetic resonance imaging (fMRI) methods as a noninvasive means to detect effects of tyrosine depletion on dopamine function. Methods: Changes in blood-oxgenation level dependent (BOLD) contrast induced by administration of the dopamine-releasing agent, amphetamine (3 mg/kg i.v.), were measured in halothane-anaesthetised rats. Results: Amphetamine evoked changes in BOLD signal intensity with the greatest effects observed in the nucleus accumbens (-7.7%), prefrontal cortex (-13.6%), and motor cortex (+12.5%). Pretreatment with a tyrosine-free amino acid mixture attenuated the response to amphetamine in some regions (nucleus accumbens and prefrontal cortex), but not others (motor cortex). Amphetamine itself had no effect in thalamus and hippocampus but, surprisingly, increased the BOLD signal after the amino acid mixture. Conclusion: These experiments demonstrate that amphetamine evokes region-specific changes in the BOLD signal in rats, and that this effect is attenuated in some but not all regions by tyrosine depletion. The data support the application of fMRI techniques for studying the effects of tyrosine depletion on dopamine function in animals and also humans.