scholarly journals Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum

2003 ◽  
Vol 23 (3) ◽  
pp. 285-300 ◽  
Author(s):  
Diana Martinez ◽  
Mark Slifstein ◽  
Allegra Broft ◽  
Osama Mawlawi ◽  
Dah-Ren Hwang ◽  
...  

The human striatum is functionally organized into limbic, associative, and sensorimotor subdivisions, which process information related to emotional, cognitive, and motor function. Dopamine projections ascending from the midbrain provide important modulatory input to these striatal subregions. The aim of this study was to compare activation of dopamine D2 receptors after amphetamine administration in the functional subdivisions of the human striatum. D2 receptor availability (V3″) was measured with positron emission tomography and [11C]raclopride in 14 healthy volunteers under control conditions and after the intravenous administration of amphetamine (0.3 mg/kg). For each condition, [11C]raclopride was administered as a priming bolus followed by constant infusion, and measurements of D2 receptor availability were obtained under sustained binding equilibrium conditions. Amphetamine induced a significantly larger reduction in D2 receptor availability (ΔV3″) in limbic (ventral striatum, −15.3 ± 11.8%) and sensorimotor (postcommissural putamen, −16.1 ± 9.6%) regions compared with associative regions (caudate and precommissural putamen, −8.1 ± 7.2%). Results of this region-of-interest analysis were confirmed by a voxel-based analysis. Correction for the partial volume effect showed even greater differences in ΔV3″ between limbic (−17.8 ± 13.8%), sensorimotor (−16.6 ± 9.9%), and associative regions (−7.5 ± 7.5%). The increase in euphoria reported by subjects after amphetamine was associated with larger ΔV3″ in the limbic and sensorimotor regions, but not in the associative regions. These results show significant differences in the dopamine response to amphetamine between the functional subdivisions of the human striatum. The mechanisms potentially accounting for these regional differences in amphetamine-induced dopamine release within the striatum remain to be elucidated, but may be related to the asymmetrical feed-forward influences mediating the integration of limbic, cognitive, and sensorimotor striatal function via dopamine cell territories in the ventral midbrain.

1991 ◽  
Vol 14 ◽  
pp. S128
Author(s):  
Yasuyoshi Watanabe ◽  
Per Hartvig ◽  
Joakim Tedroff ◽  
Peter Bjurling ◽  
Hirotaka Onoe ◽  
...  

2004 ◽  
Vol 24 (9) ◽  
pp. 1037-1045 ◽  
Author(s):  
Lars H. Pinborg ◽  
Karen H. Adams ◽  
Stig Yndgaard ◽  
Steen G. Hasselbalch ◽  
Søren Holm ◽  
...  

The aim of the present study was to develop an experimental paradigm for the study of serotonergic neurotransmission in humans using positron emission tomography and the 5-HT2A selective radioligand [18F]altanserin. [18F]altanserin studies were conducted in seven subjects using the bolus/infusion approach designed for attaining steady state in blood and brain 2 hours after the initial [18F]altanserin administration. Three hours after commencement of radiotracer administration, 0.25 mg/kg of the selective serotonin reuptake inhibitor, citalopram (Lundbeck, Valby, Denmark), was administered to all subjects as a constant infusion for 20 minutes. To reduce 5-HT1A–mediated autoinhibition of cortical 5-HT release, four of the seven subjects were pretreated with the partial 5-HT1A agonist pindolol for 3 days at an increasing oral dose (25 mg on the day of scanning). In each subject, the baseline condition (120 to 180 minutes) was compared with the stimulated condition (195 to 300 minutes). Despite a pronounced increase in plasma prolactin and two subjects reporting hot flushes compatible with an 5-HT–induced adverse effect, cortical [18F]altanserin binding was insensitive to the citalopram challenge, even after pindolol pretreatment. The biochemical and cellular events possibly affecting the unsuccessful translation of the citalopram/pindolol challenge into a change in 5-HT2A receptor binding of [18F]altanserin are discussed.


2019 ◽  
Vol 40 (4) ◽  
pp. 860-874
Author(s):  
Ansel T Hillmer ◽  
Richard E Carson

In some positron emission tomography (PET) studies, a reversibly binding radioligand is administered as a constant infusion to establish true equilibrium for quantification. This approach reduces scanning time and simplifies data analysis, but assumes similar behavior of the radioligand in plasma across the study population to establish true equilibrium in all subjects. Bias in outcome measurements can result if this assumption is not met. This work developed and validated a correction that reduces bias in total distribution volume ( VT) estimates when true equilibrium is not present. This correction, termed tissue clearance correction (TCC), took the form [Formula: see text], where β is the radioligand clearance rate in tissue, γ is a radiotracer-specific constant, and VT(A) is the apparent VT. Simulations characterized the robustness of TCC across imperfect values of γ and β and demonstrated reduction to false positive rates. This approach was validated with human infusion data for three radiotracers: [18F]FPEB, (−)-[18F]flubatine, and [11C]UCB-J. TCC reduced bias in VT estimates for all radiotracers and significantly reduced intersubject variance in VT for [18F]FPEB data in some brain regions. Thus, TCC improves quantification of data acquired from PET infusion studies.


2002 ◽  
Vol 93 (3) ◽  
pp. 1104-1114 ◽  
Author(s):  
Gaetano G. Galletti ◽  
José G. Venegas

To determine the spatial distributions of pulmonary perfusion, shunt, and ventilation, we developed a compartmental model of regional 13N-labeled molecular nitrogen (13NN) kinetics measured from positron emission tomography (PET) images. The model features a compartment for right heart and pulmonary vasculature and two compartments for each region of interest: 1) aerated alveolar units and 2) alveolar units with no gas content (shunting). The model was tested on PET data from normal animals (dogs and sheep) and from animals with experimentally injured lungs simulating acute respiratory distress syndrome. The analysis yielded estimates of regional perfusion, shunt fraction, and specific ventilation with excellent goodness-of-fit to the data ( R 2 > 0.99). Model parameters were estimated to within 10% accuracy in the presence of exaggerated levels of experimental noise by using a Monte Carlo sensitivity analysis. Main advantages of the present model are that 1) it separates intraregional blood flow to aerated alveolar units from that shunting across nonaerated units and 2) it accounts and corrects for intraregional tracer removal by shunting blood when estimating ventilation from subsequent washout of tracer. The model was thus found to provide estimates of regional parameters of pulmonary function in sizes of lung regions that could potentially approach the intrinsic resolution for PET images of 13NN in lung (∼7.0 mm for a multiring PET camera).


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