Imaging dopamine transmission in the frontal cortex: a simultaneous microdialysis and [11C]FLB 457 PET study
| Autor: | James Ruszkiewicz, Kate Gurnsey, Brian J. Lopresti, N.S. Mason, Hank P. Jedema, Charles W. Bradberry, Rajesh Narendran, W.G. Frankle, Chi-Min Chen, Lora Deuitch |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Positron emission tomography Microdialysis Pyrrolidines Frontal cortex microdialysis Dopamine Dopamine Agents Synaptic Transmission Article Radioligand Assay 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Salicylamides medicine Animals Amphetamine Dopamine metabolism Molecular Biology 030304 developmental biology Raclopride 0303 health sciences medicine.diagnostic_test Chemistry Functional Neuroimaging Macaca mulatta Corpus Striatum Frontal Lobe Psychiatry and Mental health Frontal lobe Positron-Emission Tomography Dopamine Antagonists Neuroscience 030217 neurology & neurosurgery [11C]FLB 457 medicine.drug |
| Zdroj: | Molecular psychiatry |
| ISSN: | 1476-5578 1359-4184 |
| Popis: | In a recent human positron emission tomography (PET) study we demonstrated the ability to detect amphetamine-induced dopamine (DA) release in the prefrontal cortex as a reduction in the binding of the DA D(2/3) radioligand [(11)C]FLB 457. A key requirement for validating this paradigm for use in clinical studies is demonstrating that the changes in [(11)C]FLB 457 binding observed with PET following amphetamine are related to changes in dialysate DA concentration as measured with microdialysis. Microdialysis and PET experiments were performed to compare, in five rhesus monkeys, amphetamine-induced DA release and [(11)C]FLB 457 displacement in the frontal cortex after three doses of amphetamine (0.3 mg kg(-1), 0.5 mg kg(-1) and 1.0 mg kg(-1)). Amphetamine led to a significant dose-dependent increase in dialysate (0.3 mg kg(-1): 999±287%; 0.5 mg kg(-1): 1320±432%; 1.0 mg kg(-1): 2355±1026%) as measured with microdialysis and decrease in [(11)C]FLB 457 binding potential (BP(ND), 0.3 mg kg(-1): -6±6%; 0.5 mg kg(-1): -16±4%; 1.0 mg kg(-1): -24±2%) as measured with PET. The relationship between amphetamine-induced peak ΔDA and Δ[(11)C]FLB 457 BP(ND) in the frontal cortex was linear. The results of this study clearly demonstrate that the magnitude of dialysate DA release is correlated with the magnitude of the reduction in [(11)C]FLB 457 BP(ND) in the frontal cortex. The use of the [(11)C]FLB 457-amphetamine imaging paradigm in humans should allow for characterization of prefrontal cortical DA release in neuropsychiatric disorders such as schizophrenia and addiction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|