Serotonin modulation of cerebral blood flow measured with positron emission tomography (PET) in humans

To develop a method to measure the dynamic response of the serotonin system in vivo, the effects of intravenously administered citalopram (the most selective of the serotonin reuptake inhibitors) or clomipramine on cerebral blood flow (CBF) were evaluated. CBF was measured with positron emission tomography (PET) in 27 normal subjects scanned under baseline conditions and, on the same day, after an intravenous (IV) infusion of placebo, citalopram, or clomipramine using a randomized, double-blind design. The main effects of the drugs on blood flow occurred in the thalamus, hypothalamus, and cingulate cortex. Compared to placebo, clomipramine reduced blood flow in the mediodorsal and ventral lateral nuclei of the thalamus, whereas citalopram reduced blood flow in the pulvinar nucleus and the hypothalamus. Compared to clomipramine, citalopram decreased blood flow in the cingulate cortex. The findings support previous reports showing acute central effects of citalopram and clomipramine on regional serotonergic functions measured by PET. Acute side effects may, however, require that care is taken in the selection of experimental designs for future PET studies using IV administration of these antidepressants.     

Serotonin modulation of cerebral glucose metabolism: Sex and age effects

The serotonin system is implicated in a variety of psychiatric disorders whose clinical presentation and response to treatment differ between males and females, as well as with aging. However, human neurobiological studies are limited. Sex differences in the cerebral metabolic response to an increase in serotonin concentrations were measured, as well as the effect of aging, in men compared to women. Thirty‐three normal healthy individuals (14 men/19 women, age range 20–79 years) underwent two resting positron emission tomography studies with the radiotracer [18F]‐2‐deoxy‐2‐fluoro‐D‐glucose ([¹⁸F]‐FDG) after placebo and selective serotonin reuptake inhibitor (SSRI, citalopram) infusions on two separate days. Results indicated that women demonstrated widespread areas of increased cortical glucose metabolism with fewer areas of decrease in metabolism in response to citalopram. Men, in contrast, demonstrated several regions of decreased cortical metabolism, but no regions of increased metabolism. Age was associated with greater increases in women and greater decreases in men in most brain regions. These results support prior studies indicating that serotonin function differs in men and women across the lifespan. Future studies aimed at characterizing the influences of age and sex on the serotonin system in patients with psychiatric disorders are needed to elucidate the relationship between sex and age differences in brain chemistry and associated differences in symptom presentation and treatment response. Synapse 66:955–964, 2012. © 2012 Wiley Periodicals, Inc.     

Selective serotonin reuptake inhibitor (SSRI) modulation of striatal dopamine measured with [11C]-raclopride and positron emission tomography

The effect of a pharmacologic increase in serotonin concentrations on striatal dopamine (D2) receptor availability has been measured in several studies using positron emission tomography (PET) and the radiotracer [11C]-raclopride as a method for the in vivo imaging of serotonin modulation of striatal dopamine in human subjects. These studies have shown that an acute increase in serotonin concentrations produced a decrease in striatal D2 receptor availability. The current study was undertaken to measure the effects of a more pharmacologically selective serotonergic agent compared to previous studies, the serotonin reuptake inhibitor, citalopram, on striatal D2 receptor availability. Twelve healthy control subjects underwent two PET scans performed on the same day following i.v. administration of saline (Scan 1) and citalopram (Scan 2, 40 mg, i.v.). The [11C]-raclopride data were analyzed with a graphical analysis method using the cerebellum as the input function. Plasma levels of citalopram, cortisol, and prolactin were measured. The citalopram concentrations peaked at the end of infusion (EOI) and remained relatively consistent from 30 min to 3 h postinfusion. An increase in cortisol and prolactin concentrations was observed from the EOI until 60 min after the EOI. A significant decrease in striatal D2 receptor availability was observed after citalopram infusion (-5%), presumably due to an increase in endogenous dopamine concentrations. In summary, i.v. administration of the selective serotonin reuptake inhibitor, citalopram, produced modest reductions in striatal D2 receptor availability, consistent with other human [11C]-raclopride studies using less pharmacologically selective serotonergic agents.     

Distinct functional networks associated with improvement of affective symptoms and cognitive function during citalopram treatment in geriatric depression

Variability in the affective and cognitive symptom response to antidepressant treatment has been observed in geriatric depression. The underlying neural circuitry is poorly understood. This study evaluated the cerebral glucose metabolic effects of citalopram treatment and applied multivariate, functional connectivity analyses to identify brain networks associated with improvements in affective symptoms and cognitive function. Sixteen geriatric depressed patients underwent resting positron emission tomography (PET) studies of cerebral glucose metabolism and assessment of affective symptoms and cognitive function before and after 8 weeks of selective serotonin reuptake inhibitor treatment (citalopram). Voxel-wise analyses of the normalized glucose metabolic data showed decreased cerebral metabolism during citalopram treatment in the anterior cingulate gyrus, middle temporal gyrus, precuneus, amygdala, and parahippocampal gyrus. Increased metabolism was observed in the putamen, occipital cortex, and cerebellum. Functional connectivity analyses revealed two networks which were uniquely associated with improvement of affective symptoms and cognitive function during treatment. A subcortical-limbic-frontal network was associated with improvement in affect (depression and anxiety), while a medial temporal-parietal-frontal network was associated with improvement in cognition (immediate verbal learning/memory and verbal fluency). The regions that comprise the cognitive network overlap with the regions that are affected in Alzheimer's dementia. Thus, alterations in specific brain networks associated with improvement of affective symptoms and cognitive function are observed during citalopram treatment in geriatric depression.     

Reduced postnatal cerebral glucose metabolism measured by PET after asphyxia in near term fetal lambs.

The effects of fetal asphyxia on cerebral function and development, involve the transition from fetal to neonatal life. Changes in cerebral glucose metabolism may be an early postnatal indicator of fetal asphyxia. The objective is to develop an experimental lamb model involving the transition from fetal to neonatal life and to examine the effect of fetal asphyxia with cerebral hypoxic ischemia on early postnatal cerebral glucose metabolism. Fetal asphyxia was induced by total umbilical cord occlusion in eight near-term fetal lambs (134-138 days) with the ewe under isoflurane-opiate anesthesia. The mean occlusion time until cardiac arrest was 14.5 (4.2) min (SD). Lambs were immediately delivered and standardized resuscitation was instituted after 2 min asystole. At 4 hr postnatal age, [18-F]Fluoro-2-deoxy-glucose (18-FDG) was injected intravenously in eight asphyxiated lambs and in eight controls. Cerebral glucose metabolism was examined by positron emission tomography (PET). As a result the mean arterial blood pressure, acid-base values, blood glucose and serum lactate at 4 hr postnatal age did not differ significantly between lambs subjected to umbilical cord occlusion and controls. EEG was abnormal in all lambs subjected to cord occlusion and normal in the controls at 4 hr postnatal age. Global cerebral metabolic rate (CMRgl) as determined by PET was significantly lower in lambs subjected to cord occlusion mean/median (SD) 22.2/19.6 (8.4) micromol/min/100 g) than in controls mean/median (SD) 37.8/35.9 (6.1); P < 0.01). Global CMRgl is significantly reduced in newborn lambs 4 hr after fetal asphyxia induced by umbilical cord occlusion. A reduction in CMRgl is an early indicator of global hypoxic cerebral ischemia.     

Test–retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test–retest variability of the binding of [¹⁸F]altanserin were measured as important steps in the further development of [¹⁸F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT_2A receptor. Two high specific activity [¹⁸F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2–16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [¹⁸F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16–20%). For all regions, the absolute value of the test–retest differences in the Logan DV values averaged 12% or less. The test–retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [¹⁸F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT_2A receptors determined by postmortem autoradiographic studies (r² = 0.95, P < 0.001 for the 4C model and r² = 0.96, P < 0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [¹⁸F]altanserin (present at levels of 3–25% of the total radioactivity in human plasma 10–120 min postinjection) were able to penetrate the blood–brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT_2A receptor and did not interfere with the interpretation of regional [¹⁸F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test–retest variability of [¹⁸F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [¹⁸F]altanserin in human brain was correlated with the known regional distribution of 5-HT_2A receptors. These findings support the usefulness of [¹⁸F]altanserin as a radioligand for PET studies of 5-HT_2A receptors. Synapse 30:380–392, 1998. © 1998 Wiley-Liss, Inc.     

Membranous lipodystrophy presenting with palilalia: a PET study of cerebral glucose metabolism

A case of membranous lipodystrophy (Nasu-Hakola disease; NHD) associated with palilalia was reported. A 38-year-old Japanese woman developed walking difficulty in her twenties. At age 35 she manifested neuropsychiatric symptoms characterized by euphoria, palilalia and dementia. A bone marrow biopsy showed periodic acid Schiff-positive membranous cystic lesions in the adipose tissue. Positron emission tomography with (18F)-2-fluoro-2-deoxy-D-glucose disclosed that regional cerebral glucose metabolism was decreased in the bilateral frontal white matter with mild hypometabolism in the thalamus and basal ganglia; all predominantly on the right. Taken together with the previous postmortem findings, it is postulated that frontal lobe hypofunction, predominantly in the right hemisphere, produced the unique neuropsychiatric symptoms in this patient.     

Glucose metabolism and rate constants in Alzheimer''s disease examined with dynamic positron emission tomography scan

Glucose metabolic rate constants in patients with Alzheimer's disease were analyzed using dynamic positron emission tomography with [18-F] fluoro-2-deoxyglucose (FDG). The cerebral metabolic rate of glucose (CMRG) was calculated using obtained rate constants, as well as the autoradiographic method. The half-life and distribution volume of FDG between the blood and the brain tissue were also calculated from obtained metabolic rate constants. The most severely affected metabolic step was the phosphorylation of glucose in the parietotemporal regions. The distribution volume of FDG showed no remarkable deviation from normal controls, while the half-life of FDG was found to be longer in the parietal and temporal regions. The CMRG from rate constants and that from the autoradiographic method showed no remarkable differences.     

Positron emission tomography in ischaemic stroke: cerebral perfusion and metabolism after stroke onset

PET studies were performed in 37 patients up to 1 month after ischaemic stroke to observe the relationships between cerebral blood flow (CBF), rate of cerebral oxygen metabolism (CMRO(2)) and oxygen extraction fraction (OEF) with time. PET findings were classified as misery perfusion (two patients), luxury perfusion (15 patients), matched hypoperfusion-hypometabolism (17 patients) or normal (nine patients). Misery perfusion was seen up to 3 days post-stroke, suggesting an extended time window during which at least some tissue may be salvageable. Luxury perfusion, an indication of non-nutritional flow, was seen as early as 30 h and as late as 23 days, but more commonly between 3 and 7 days. A matched reduction of CBF and CMRO(2) was seen during all time periods, but as early as 27 hours. Since this was associated with severely impaired CBF, presumably from the onset of stroke, it can be assumed that the duration of cerebral tissue survival is less than 27 h under these conditions. We inferred that, for maximal tissue recovery, therapy will need to be introduced within 27 h after stroke, but that at least some potential for recovery exists up to 3 days.     

Serotonin 1B receptor density mapping of the human brainstem using positron emission tomography and autoradiography

The serotonin 1B (5-HT_1B) receptor has lately received considerable interest in relation to psychiatric and neurological diseases, partly due to findings based on quantification using Positron Emission Tomography (PET). Although the brainstem is an important structure in this regard, PET radioligand binding quantification in brainstem areas often shows poor reliability. This study aims to improve PET quantification of 5-HT_1B receptor binding in the brainstem.Volumes of interest (VOIs) were selected based on a 3D [³H]AZ10419369 Autoradiography brainstem model, which visualized 5-HT_1B receptor distribution in high resolution. Two previously developed VOI delineation methods were tested and compared to a conventional manual method. For a method based on template data, a [¹¹C]AZ10419369 PET template was created by averaging parametric binding potential (BP_ND) images of 52 healthy subjects. VOIs were generated based on a predefined volume and BP_ND thresholding and subsequently applied to test-retest [¹¹C]AZ10419369 parametric BP_ND images of 8 healthy subjects. For a method based on individual subject data, VOIs were generated directly on each individual parametric image.Both methods showed improved reliability compared to a conventional manual VOI. The VOIs created with [¹¹C]AZ10419369 template data can be automatically applied to future PET studies measuring 5-HT_1B receptor binding in the brainstem.     

PET determination of regional cerebral glucose metabolism in alcohol-dependent men and healthy controls using 11C-glucose

Regional brain glucose metabolism was determined in 9 male alcohol-dependent inpatients and 12 male healthy controls. All the patients were socially impaired by the alcohol abuse. All the subjects had abstained from alcohol and drugs for more than four weeks before entering the study. Brain glucose metabolism was determined by positron emission tomography (PET) with 11C-glucose as the tracer. Regions of interest were drawn on displayed computed tomographic (CT) images of the brain. Regions were transferred to corresponding PET slices, allowing the determination of regional glucose metabolism. In the healthy volunteers there was a reduction in glucose metabolism with age. In 11 of the 19 brain regions examined, the alcoholics had a 20% to 30% lower glucose metabolism than the controls. This was true for both cortical and subcortical structures. The distribution of relative regional metabolic rates indicated that parietal cortical areas were most affected. Atrophic changes as shown by CT were not correlated to the reduced metabolism in the alcohol-dependent patients.     

Cerebral glucose metabolism on positron emission tomography of children

Establishing the normative range of age‐dependent fluorodeoxyglucose (FDG) uptake in the developing brain is necessary for understanding regional quantitative analysis of positron emission tomography (PET) brain images in children and also to provide functional information on brain development. We analyzed head sections of FDG PET/computed tomography (CT) images for 115 patients (5 months to 23 years) without central nervous system disease before treatment, as PET studies are not performed on healthy children owing to ethical considerations and the risk of radiation exposure. We investigated the changes in FDG uptake and established age‐associated normative ranges of cerebral FDG. Head sections of FDG PET/CT images were registered to a population‐based probabilistic atlas of human cortical structures. Gray matter of 56 brain structures was defined on normalized PET images according to the atlas. To avoid individual and experimental confounding factors, the relative standardized uptake value (SUV) over the cerebellum of each structure was calculated. Relative SUVs were analyzed by ANOVA and modeled using generalized estimating equalization analysis with false discovery rate control. Age and structure were significant factors affecting SUVs. Anatomic proximity had little effect on FDG uptake. Linear and quadratic developmental trajectories were observed on absolute and relative SUVs, respectively. An increase from posterior‐to‐anterior and superior‐to‐inferior pattern was observed in both absolute SUV increase rate and relative SUV peak age. The SUV of each structure was modeled with respect to age, and these models can serve as baselines for the quantitative analysis of cerebral FDG–PET images of children. Hum Brain Mapp 35:2297–2309, 2014. © 2013 Wiley Periodicals, Inc .     

Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study

The aim of this study was to examine the hypothesis, if the activation of some cerebral structures due to physiological stimulation is accompanied by deactivations of other structures elsewhere in the brain. A vibratory stimulus was applied to the right hand palm of healthy volunteers and the regional cerebral blood flow (rCBF) and regional cerebral oxygen metabolism (rCMRO2) were measured with positron emission tomography (PET). Regional analysis and voxel-by-voxel plots indicated that the stimulation induced increases and decreases of the rCBF were coupled to increases and decreases of the rCMRO2. The increases were localized in the left primary somatosensory area (SI), the left secondary somatosensory area (SII), the left retroinsular field (RI), the left anterior parietal cortex, the left primary motor area (MI), and the left supplementary motor area (SMA). The decreases occurred bilaterally in the superior parietal cortex, in paralimbic association areas, and the left globus pallidus. The increases and decreases of the rCBF and rCMRO2 were balanced in such a way that the mean global CBF and CMRO2 did not change compared with rest. We conclude that the decreases of the cerebral oxidative metabolism indicated regional depressions of synaptic activity.     

18F-DG PET在癫痫外科手术中的评价

目的评估^18F-脱氧葡萄糖（^18F-DG）正电子发射X线体层照像术（PET）对癫痫外科治疗的指导意义。方法对22例顽同性癫痫的患者进行^18F-DGPET、长程脑电图（EEG）、MRI检查，并根据检查结果进行开颅手术治疗。手术后对切除组织进行病理检查，并对患者进行手术后随访评估。结果所有患者PET检查均为阳性，20例患者（90．9％）长程脑电图检查阳性，18例患者（81．8％）MRI检查阳性，20例患者（90．9％）手术后癫痫发作部分或完全缓解，2例患者（9．1％）无明显缓解。结论^18F-DGPET在癫痫灶定位方面的作用对手术有重要指导意义，术中皮质脑电图（ECoG）将有助于提高手术治疗的效果。     

Effects of ketamine/xylazine and isoflurane on rat brain glucose metabolism measured by 18F‐fluorodeoxyglucose‐positron emission tomography

The aim of the present study was to investigate changes in glucose metabolism in male Wistar rats induced by the anesthetics isoflurane and ketamine combined with xylazine via ¹⁸F‐fluorodeoxyglucose‐positron emission tomography. We analyzed the differential effects of the anesthetics on ¹⁸F‐fluorodeoxyglucose uptake and pharmacokinetics in 33 rats using quantification methods: (a) the standardized uptake value, (b) voxel‐based analyses, and (c) kinetic analysis. Both anesthetics reduced glucose uptake in the entire brain. The voxel‐based analyses detected smaller uptake reductions in the bilateral primary somatosensory system cortex and part of the limbic system in the ketamine‐xylazine (KX) group and in the vestibular nucleus in the isoflurane group. Through kinetic analysis, we found that the volume of distribution and the membrane transport rate K₁ were reduced in the KX group. Through various methods of ¹⁸F‐fluorodeoxyglucose‐positron emission tomography quantification, the present study found that anesthesia with the ketamine‐xylazine combination induced a global reduction of glucose metabolism compared with isoflurane; this reduction of metabolism was relatively lower in the primary somatosensory cortex and part of the limbic system. The volume of distribution of ¹⁸F‐fluorodeoxyglucose and its Glut1‐mediated transport across the brain membranes (K₁) were decreased in the KX group.     

A proposed method for the determination of cerebral regional intermediary glucose metabolism in humans in vivo using specifically labeled 11C-glucose and positron emission transverse tomography (PETT). I. An animal model with 14C-glucose and rat brain autoradiography

Based upon data obtained with our arterio-venous technique for the determination of cerebral metabolism in humans in vivo we have proposed a method for the determination of cerebral regional intermediary glucose metabolism in humans in vivo using specifically labeled ¹¹C-glucose and positron emission transverse tomography (PETT). In it we would give the subject successive intravenous injections of [3,4-¹¹C] glucose, [2,5-¹¹C] glucose and [1-¹¹C] glucose. There would be a 30 min period of continuous PETT measurements following each injection and a 2 hr interval after the first and second injections. The data would be used with suitable equations and algorithms to estimate for each specific region of the subject's brain the dynamics of the Embden-Meyerhof-Parnas (EMP) and the tricarboxylic acid cycle (TCA) metabolic pathways and the incorporation of glucose carbons into lactate, and the extent of dilution of glucose carbons in traversing the TCA with their subsequent incorporation into other carbon pools of the brain (ie, glutamate, glutamine, GABA, alanine). Using ¹⁴C as a model for ¹¹C and autoradiographs made with rat brain slices, we have produced an animal model to demonstrate the feasibility of our proposed method. The resulting autoradiographs have provided evidence of the validity of the predictions made from our arterio-venous data. The model was employed to show the selective reductions in the rates of incorporation of specific carbon atoms of glucose into regions of the rat brain and evidence of altered metabolic pathways following a single electroconvulsive shock (ECS) and after a series of nine ECS.     

Serotonin transporter binding in bipolar disorder assessed using [11C]DASB and positron emission tomography.

BACKGROUND: Evidence from neuroimaging post-mortem, and genetic studies suggests that bipolar disorder (BD) is associated with abnormalities of the serotonin-transporter (5-HTT) system. Because of various limitations of these studies, however, it has remained unclear whether 5-HTT binding is abnormal in unmedicated BD-subjects. This study used PET and [(11)C]DASB, a radioligand that afforded higher sensitivity and specificity for the 5-HTT than previously available radioligands, to compare 5-HTT binding between BD and control subjects. METHODS: The 5-HTT binding-potential (BP) was assessed in 18 currently-depressed, unmedicated BD-subjects and 37 healthy controls using PET and [(11)C]DASB. RESULTS: In BD, the mean 5-HTT BP was increased in thalamus, dorsal cingulate cortex (DCC), medial prefrontal cortex and insula and decreased in the brainstem at the level of the pontine raphe-nuclei. Anxiety ratings correlated positively with 5-HTT BP in insula and DCC, and BP in these regions was higher in subjects manifesting pathological obsessions and compulsions relative to BD-subjects lacking such symptoms. Subjects with a history of suicide attempts showed reduced 5-HTT binding in the midbrain and increased binding in anterior cingulate cortex versus controls and to BD-subjects without attempts. CONCLUSIONS: This is the first study to report abnormalities in 5-HTT binding in unmedicated BD-subjects. The direction of abnormality in the brainstem was opposite to that found in the cortex, thalamus, and striatum. Elevated 5-HTT binding in the cortex may be related to anxiety symptoms and syndromes associated with BD.     

Correlation of brain cell glucose metabolism and patient's condition in children with epileptic encephalopathy An assessment using fluorine-18-fluoro-2-deoxy-D-glucose positron emission computed tomography

We examined a total of 16 children with epileptic encephalopathy using fluo-rine-18-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission computed tomography (PET), magnetic resonance imaging (MRI) and electroencephalography. Children with infantile spasms showed significant mental retardation, severely abnormal electroencephalogram recordings, and bilateral diffuse cerebral cortex hypometabolism with 18F-FDG PET imaging. MRI in these cases showed brain atrophy, multi-micropolygyria, macrogyria, and porencephalia. In cases with Len-nox-Gastaut syndrome, 18F-FDG PET showed bilateral diffuse glucose hypometabolism, while MRI showed cortical atrophy, heterotopic gray matter and tuberous sclerosis. MRI in cases with myoclonic encephalopathy demonstrated bilateral frontal and temporal cortical and white matter atrophy and 18F-FDG PET imaging showed bilateral frontal lobe atrophy with reduced bilateral frontal cortex, occipital cortex, temporal cortex and cerebellar glucose uptake. In children who could not be clearly classified, MRI demonstrated cerebral cortical atrophy and 18F-FDG PET exhibited multifocal glucose hypometabolism. Overall, this study demonstrated that the degree of brain metabolic abnormality was consistent with clinical seizure severity. In addition, 18F-FDG PET imaging after treatment was consistent with clinical outcomes. These findings indicate that 18F-FDG PET can be used to assess the severity of brain injury and prognosis in children with epileptic encephalopathy.     

Effect on [11C]DASB binding after tranylcypromine-induced increase in serotonin concentration: positron emission tomography studies in monkeys and rats

Several research groups have demonstrated that under specific conditions, in vivo neuroreceptor binding techniques can be used to measure acute changes in the concentrations of endogenous transmitters in the vicinity of neuroreceptors. The aim of this study was to investigate whether [(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([(11)C]DASB) binding to the plasma membrane serotonin transporter (SERT) in the rhesus monkey and rat brain decreased after a pharmacologically-induced increase in the interstitial serotonin (5HT) concentration. Three rhesus monkeys were given repeated single boluses of [(11)C]DASB in sequential positron emission tomography (PET) experiments. Rats were given the tracer as a bolus dose plus a constant infusion. In vivo binding in both models was studied before and after presumably having increased interstitial 5HT concentrations using tranylcypromine (TCP), which inhibits the enzyme (monoamine oxidase, MAO), that degrades 5HT. The rat brain tissue was analyzed using high-performance liquid chromatography (HPLC) to determine the proportion of the PET signal comprising unchanged [(11)C]DASB. The binding of [(11)C]DASB in the thalamus decreased in both rhesus monkeys and rats after TCP administration. The possibility of using [(11)C]DASB as a tool for monitoring changes in endogenous serotonin concentrations merits further investigation.