Brain Serotonin Synthesis Rates in Rhesus Monkeys Determined by [11C]α-Methyl-?-Tryptophan and Positron Emission Tomography Compared to CSF 5-Hydroxyindole-3-Acetic Acid Concentrations

Abstract

Twelve male, fasted, anesthetized rhesus monkeys were studied with positron emission tomography (PET) and [ C] ␣ -methyl-L -tryptophan ( ␣ MTP) to determine serotonin synthesis rates as described by Diksic et al. (1991) (Nishizawa et al. 1997) and dogs (Diksic et al. 1991) Early attempts to determine serotonin synthesis rates in small mammals usually involved pharmacological manipulation of the serotonin system followed by the sampling of brain tissue for the determination of tryptophan, tryptophan metabolites, serotonin, and/or serotonin metabolites. These studies were limited by the ability of the investigator to isolate specific brain regions, and the sensitivity of the assays usually required the pooling of tissues from multiple animals (Colmenares et al. 1975;Curzon and Marsden 1975;Fernstrom and Wurtman 1971; From the Laboratory of Clinical Studies (SES, DH, WW, JDH, ML), DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda; and the PET Department (RC, BS, PH, WE), National

The Suitability of [11C]-α-Methyl-L-tryptophan as a Tracer for Serotonin Synthesis: Studies With Dual Administration of [11C] and [14C] Labeled Tracer

“…No significant differences were seen between runs; thus, there was no measurable effect of the additional unlabeled rxMTP on the tracer uptake, as expected, or an effect of prolonged anesthesia. None of the regional K* values were significantly different from those given by Shoaf et al (1998).…”

“…Free and total plasma tryptophan concentrations were deter mined by HPLC with fluorometric detection according to Shoaf et al (1998).…”

“…Patlak plots of PET data from mon keys, between 60 and 90 minutes, provide lower esti mates of exM5HT, but the values predicted still are higher than would be expected from the rat data. This inconsis tency between measurements of metabolized tracer and the model predictions of serotonin synthesis rate sug gests that the model estimates are incorrect, perhaps be cause the time for the precursor pool to reach equilibrium is significantly longer than previously estimated (Shoaf et al, 1998;Gharib et ai., 1999).…”

Differential Behavioral Effects of Plasma Tryptophan Depletion and Loading in Aggressive and Nonaggressive Men

“…Moreover, in the aggressive men, aggressive responses under Trp-loaded conditions correlated negatively with plasma concentrations of free (but not total) Trp. This reflects PET scan findings in monkeys that rates of brain 5-HT (analogue) synthesis correlate with plasma concentrations of free Trp but not total Trp (Shoaf et al 1998). Conversely, in nonaggressive men (who attained higher plasma Trp concentrations), post-loading plasma Trp tended to show a positive relationship with aggression.…”

5-Hydroxy-l-[β-11C]tryptophan versus α-[11C]Methyl-l-tryptophan for Positron Emission Tomography Imaging of Serotonin Synthesis Capacity in the Rhesus Monkey Brain

“…In the present study, the total radioactivity concentration among brain regions (except for the striatum) was 30% to 50% higher for [ ]AMT, which also reflects the higher influx and radioactivity trapping for the former tracer. Shoaf et al (1998Shoaf et al ( , 2000 and Gharib et al (1999) argued that […”