Reduction of Brain Dopamine Concentration With Dietary Tyrosine Plus Phenylalanine Depletion: An [¹¹C]Raclopride PET Study

Abstract

This is the first demonstration of an effect of a dietary manipulation on brain dopamine release in humans. This result provides support for the further investigation of the role of dietary manipulations in the treatment of neuropsychiatric disorders.

Lack of Effect of Tyrosine Depletion on Mood in Recovered Depressed Women

“…Indeed in a recent PET imaging of TYR depletion, we found that the increase in D 2 receptor binding as measured by [ 11 C]raclopride correlated significantly with the fall in the plasma ratio of TYR and PHE to large neutral amino acids (Montgomery et al, 2003). A similar finding was reported by Leyton et al (2004) who found that the ability of TYR depletion to attenuate the decrease in [ 11 C]raclopride binding produced by d-amphetamine correlated linearly with reduction in plasma TYR levels.…”

“…Although administration of the BAL mixture increases plasma levels of PHE and TYR, (Sheehan et al, 1996) overall, as found in the present study, it produces some lowering in the plasma ratio of TYR þ PHE : BCAA Montgomery et al, 2003). For reasons that are not clear, the extent of this reduction varies somewhat between studies but it is always substantially less than that produced by the TYR-free mixture.…”

“…AMPT treatment is, of course, a different pharmacological procedure to that of TYR depletion. For example, unlike TYR depletion, AMPT can produce extrapyramidal movement disorders (Booij et al, 2003) and, consistent with this, PET imaging studies of [ 11 C]raclopride displacement suggest that AMPT produces a substantially greater impairment in DA release than does TYR depletion (Laruelle et al, 1997;Montgomery et al, 2003). It is possible therefore that relative to AMPT, the impairment in DA function produced by TYR depletion is too modest to provoke clinical depressive symptomatology in vulnerable individuals.…”

“…More recently, a study using positron emission tomography (PET) demonstrated increased striatal binding of the D 2 receptor ligand, raclopride, after TYR depletion consistent with lowered presynaptic release of DA (Montgomery et al, 2003). Functionally, TYR depletion appears to disrupt basal DA function sufficiently to reduce performance on tasks of spatial recognition memory and spatial working memory , which are sensitive to DA manipulation (Elliott et al, 1997;Mehta et al, 1999).…”

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

“…Using this method, serotonin depletion was found to decrease PPI in healthy humans (Phillips et al, 2000a). On the other hand, acute tyrosine/phenylalanine depletion (ATPD) has been shown to selectively decrease dopamine synthesis and release (Jaskiw and Bongiovanni, 2004;Leyton et al, 2000;McTavish et al, 1999aMcTavish et al, , b, 2001aMehta et al, 2005;Montgomery et al, 2003), and impair dopamine-dependent cognitive processes such as working memory (Harmer et al, 2001;Harrison et al, 2004). The effects of dopamine depletion via ATPD on PPI and P50 suppression are yet to be determined.…”