• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.11a
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• pp.171-172
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• 1996

Cocaine is a powerful reinforcer that has become a popular drug of abuse in man. CNS effects that are related to the abuse of cocaine include feeling of well-being and euphoria. Brain dopamine systems are thought to mediate reinforcement and it is often assumed that cocaine's inhibition of dopamine uptake is the mechanism underlying its reinforcing effects. With increase in cocaine use among general population in recent years, adverse effects of the drug have occurred in all social strata and age groups. Therefore, it has been recognized that the epidemic of cocaine abuse is a growing major concerning public health. One of the most troubling aspects of cocaine abuse is its use by pregnant women. Drug abuse during pregnancy puts two lives at risk. Cocaine produces toxic effects on the fetus at concerntrations that are apparently nontoxic to the mother. Not only does cocaine cross the placenta via diffusion and via rapid penetration to mucous membranes, due to its high lipid solubility, but cocaine can also be found in breast milk, the effects of the cocaine can persist long after the child is born. Although it is known that prenatal cocaine exposure is associated with developmental risk to the fetus ana newborn, few studies have been conducted to assess the mechanisms whereby either short-term or long-term administration of cocaine can exert its harmful effects on the mother or the child. Therefore, it was our great interest to investigate the pharmacological and neurobehavioral changes in offspring that are prenatally exposed to cocaine.

• The Korean Journal of Nuclear Medicine
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• v.32 no.1
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• pp.10-19
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• 1998

The SPECT radiopharmaceuticals labeled with I-123 for dopamine transporter imaging have been used to measure dopamine transporters in patients with movement disorders. However, a cyclotron produced I-123 limits its availiability and ease of use as a radioisotope to be labeled with pharmaceuticals in routine clinical diagnostic procedures. Recently, new radiophannaceuticals for Tc-99m which has optimal characteristic for SPECT imaging have been developed to overcome the limits of using I-123. The purpose of this study was to compare the quality of [Tc-99m]TRODAT-1 with [I-123]IPT SPECT data and then to evaluate the usefulness of [Tc-99m]TRODAT-1 SPECT by using three noninvasive simplified quantitative methods. TRODAT-1 labeled with Tc-99m($15.93{\pm}0.82mCi$) and IPT labeled with I-123($6.60{\pm}0.11mCi$) were injected into five normal controls. Dynamic [Tc-99m]TRODAT-1 SPECT scans of brain were performed for 10 minutes each over 180 minnutes, and for 20 minutes at 4 hrs and 5 hrs. [I-123]IPT SPECT scans were performed for 5 minutes each over 120 minutes. Time activity curves were generated for the left basal ganglia(LBG), right basal ganglia(RBG), and occipital cortex(OCC). Dopamine transporter parameters were ohtained using (BG-OCC)/OCC, graphical method($R_V$), and area ratio method($R_A$). TRODAT-1 and IPT SPECT imaging showed high uptake at the level of the basal ganglia. (BG-OCC)/OCC ratios for TRODAT-1 and IPT were $0.80{\pm}0.14$, and $3.22{\pm}0.81$, $R_Vs$ were $0.62{\pm}0.12$, and $2.30{\pm}0.35$, and $R_As$ were $0.37{\pm}0.08$ and $1.73{\pm}0.31$, respectively. In conclusion, further improvement of [Tc-99m]TRODAT-1 imaging characteristics may be required to estimate the dopamine transporter concentrations in human brains although it shows clear BG localization.

• Journal of Korean Neurosurgical Society
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• v.30 no.3
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• pp.342-348
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• 2001

Objective : Dopamine transporter concentrations have been known to decrease in Parkinson's disease(PD). The aim of the present study was to evaluate the correlation between SPECT measurements of [I-123]N-(3-iodopropene-2-yl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-chlorophenyl) tropane(IPT) as an imaging agent for measuring changes in transporter concentrations with PD. Patients and Methods : IPT labelled with $4.87{\pm}1.29mCi$($180.19{\pm}47.73MBq$) of [I-123] was intravenously injected into 23 patients(age : $58{\pm}12$) with PD and three normal controls(NC)(age : $37{\pm}7$) as bolus. Brain SPECT were then performed at 1 hour and 2 hours after injection on a double headed camera. The statistical parameters were the contrast ratio of left basal ganglia(BG) and right basal ganglia to occipital cortex(OCC) per milli curies of injected radiotracer at 1 hour and 2 hours. The correlations were evaluated between these parameters and Hoehn-Yahr classification of the patients. Results : The(BG - OCC)/OCC/mCi ratios at 1 hour and 2 hours for PD and NC were $0.14{\pm}0.07$ and $0.27{\pm}0.07$(1 hour) and $0.12{\pm}0.07$ and $0.34{\pm}0.04$(2 hour), respectively. The(BG - OCC)/OCC/mCi ratios of Parkinson's disease were decreased with higher grade of Hoehn-Yahr classification of the patients. The ratio between BG and OCC for PD were clearly separated from NC and may be useful outcome measures for clinical diagnosis. Conclusion : The findings suggest that IPT may be a very useful tracer for early diagnosis and treatment of PD and study of dopamine re-uptake site.

• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.35-46
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• 1996

Dopamine transporter concentrations have been known to decrease in Parkinson's disease (PD) or increase in Tourette's disorder. The purpose of this study was to evaluate the effectiveness of [I-123]N-(3-iodopropene-2-yl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-chlorophenyl) tropane (IPT) as an imaging agent for measuring changes in transporter concentrations with PD. IPT labelled with 6.69+/-0.64 mCi(247.53+/-23.68 MBq) of I-123 was intravenously injected into ten patients(age: 55+/-11) with PD, and six normal controls(NC)(age: 46+/-14) as a bolus. Dynamic SPECT scans of the brain were then performed for 5 minutes each over 120 minutes on a triple headed camera. Time activity curves were generated for the left basal ganglia(LBG), right basal ganglia(RBC), and occipital cortex(OCC). The statistical parameters included the time to peak activity, the contrast ratio of LBG and RBG to OCC at several time points, and the accumulated specific binding counts/mCi/pixel(ASBC) from 0 to 115 minutes. The uptake of IPT in the brains of PD and NC peaked within 10 minutes of injection in all subjects. The maximum target to background ratio in the basal ganglia of PD and NC occurred at 85+/-20 min and 110+/-6 min of injection, respectively. The BG/OCC ratios at 115 minutes for PD and NC were 2.15+/-0.54 and 4.26+/-0.73, respectively. The ASBC at 115 minutes for PD and NC were 152.91+/-50.09 and 289.51+/-49.00, respectively. The ratio of BG/OCC for the NC was significantly higher than the ratio for PD. SPECT data matched with clinical diagnosis for PDs. The ratio between BG and OCC and the ASBC for PD were clearly separated from NC and may be useful outcome measures for clinical diagnosis. The findings suggest that IPT may be a very useful tracer for early diagnosis of PD and study of dopamine reuptake site.

• Korean Journal of Radiology
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• v.24 no.7
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• pp.690-697
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• 2023

Objective: ¹⁸F-FP-CIT positron emission tomography (PET) is known for its high sensitivity and specificity for evaluating striatal dopamine transporter (DAT) binding. Recently, for the early diagnose of Parkinson's disease, many researchers focused on the diagnosis of synucleinopathy in organs involved in non-motor symptoms of Parkinson's disease. We investigated the feasibility of salivary gland uptake on ¹⁸F-FP-CIT PET as a new biomarker in patients with parkinsonism. Materials and Methods: A total of 219 participants with confirmed or presumed parkinsonism, including 54 clinically diagnosed idiopathic Parkinson's disease (IPD), 59 suspected and yet undiagnosed, and 106 with secondary parkinsonism, were enrolled. The standardized uptake value ratio (SUVR) of the salivary glands was measured on both early and delayed ¹⁸F-FP-CIT PET scans using the cerebellum as the reference region. Additionally, the delayed-to-early ratio (DE_ratio) of salivary gland was obtained. The results were compared between patients with different PET patterns. Results: The SUVR in early ¹⁸F-FP-CIT PET scan was significantly higher in patients with IPD pattern compared that in the non-dopaminergic degradation group (0.5 ± 0.19 vs. 0.6 ± 0.21, P < 0.001). Compared with the non-dopaminergic degradation group, the DE_ratio was significantly lower in patients with IPD (5.05 ± 1.7 vs. 4.0 ± 1.31, P < 0.001) or atypical parkinsonism patterns (5.05 ± 1.7 vs. 3.76 ± 0.96, P < 0.05). The DE_ratio was moderately and positively correlated with striatal DAT availability in both the whole striatum (r = 0.37, P < 0.001) and posterior putamen (r = 0.36, P < 0.001). Conclusion: Parkinsonism patients with an IPD pattern exhibited a significant increase in uptake on early ¹⁸F-FP-CIT PET and a decrease in the DE_ratio in the salivary gland. Our findings suggest that salivary gland uptake of dual-phase ¹⁸F-FP-CIT PET can provide diagnostic information on DAT availability in patients with Parkinson's disease.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.88-93
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• 1994

The mechanisms controlling the intensity and duration of synaptic transmission are numerous. Once an action potential reaches a nerve terminal, the stored neurotransmitters are released in a quantum fashion into the synaptic cleft. At that point neurotransmitters can act on post-synaptic receptors to elicit an action on the post-synaptic cell or net at so-called auto-receptors that are located on the presynaptic side and which often regulate the further release of the neutotransmitter. Whereas the action of the neurotransmitter receptors is regulated by desensitization phenomenon, the major mechanism by which the intensity and duration of neurotransmitter action is presumably regulated by either its degradation or its removal from the synaptic cleft. In the central nervous system, specialized proteins located in fe plasma membrane of presynaptic terminals function to rapidly remove neurotransmitters from the synaptic cleft in a sodium chloride-dependent fashion. These proteins have been referred to as uptake sites or neurotransmitter transporters. Once taken up by the plasma membrane transporters, neurotransmitters are repackaged into secretory vesicles by distinct transporters which depend on a proton gradient.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.sup1
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• pp.177-180
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• 2008

Parkinson's disease is the second most common neurodegenerative disorder. It is slowly progressive disease that affects a small area of cells in the mid brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in a vital chemical known as dopamine. In the diagnosis of Parkinson's disease, it has difficulty in biopsy and limits in radiologic modalities. $^{18}F-FDG$ PET shows various findings from normal to diffuse decrement of FDG uptake. $^{18}F-FDG$ PET is expected to be a evaluation tool in the treatment of Parkinson's disease.

• Journal of Life Science
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• v.19 no.9
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• pp.1232-1238
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• 2009

Neurotransmitter release is regulated by various proteins of the active zone in the presynaptic nerve terminals. Dopamine (DA) is an essential neurotransmitter associated with the pathophysiology of diverse behavioral and mental illness such as schizophrenia and drug addiction. We measured synaptosomal DA release of knockout (KO) mice which lacked major genes related to neurotransmitter release. Synaptosomal DA uptake and release were performed and measured using [$^3H$]-DA and superfusion experiments. 3 of the 17 KO mice exhibited altered DA release compared to their littermate controls. In $Rim1{\alpha}$ KO, [$^3H$]-DA release evoked by membrane depolarization significantly decreased. Both basal (physiological buffer-evoked) and membrane depolarization-evoked DA release significantly decreased in dopaminergic conditional KO of $Rim1{\alpha}{\beta}$. Dopaminergic conditional KO of neurexin3 demonstrated a significant increase of membrane depolarization-evoked DA release. These data explain the similarities and distinctions between DA and other classical neurotransmitters such as glutamate and GABA ($\gamma$-aminobutyric acid) release. In conclusion, $Rim1{\alpha}$ and neurexin3 may be important regulators of presynaptic DA release and related to disorders of the nervous system.

• BMB Reports
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• v.50 no.1
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• pp.31-36
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• 2017

High-dose caffeine uptake is a developmental stressor and causes food-avoidance behavior (aversion phenotype) in C. elegans, but its mode of action is largely unknown. In this study, we investigated the molecular basis of the caffeine-induced aversion behavior in C. elegans. We found that aversion phenotype induced by 30 mM caffeine was mediated by JNK/MAPK pathway, serotonergic and dopaminergic neuroendocrine signals. In this process, the dopaminergic signaling appears to be the major pathway because the reduced aversion behavior in cat-2 mutants and mutants of JNK/MAPK pathway genes was significantly recovered by pretreatment with dopamine. RNAi depletion of hsp-16.2, a cytosolic chaperone, and cyp-35A family reduced the aversion phenotype, which was further reduced in cat-2 mutants, suggesting that dopaminergic signal is indeed dominantly required for the caffeine-induced food aversion. Our findings suggest that aversion behavior is a defense mechanism for worms to survive under the high-dose caffeine conditions.

• Anxiety and mood
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• v.19 no.2
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• pp.56-60
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• 2023

Progressive supranuclear palsy (PSP) is rare atypical Parkinsonism accompanied by various psycho-behavioural problems. In this case report, we describe the diagnostic and treatment progress of a 65-year-old PSP patient who visited the psychiatric clinic with a depressed mood and lumbar pain resulting in a suicide attempt. Over the course of 30 months of treatment, typical characteristics of PSP, such as postural instability, dyskinesia, cognitive dysfunction and supranuclear gaze palsy, became prominent, and magnetic resonance imaging and the F-18 FP-CIT positron emission tomography revealed midbrain atrophy and reduced dopamine uptake in the basal ganglia. When treating elderly patients with depression, parkinsonism symptoms such as gait disturbances, frequent falls, tremors, and rigidity should be closely examined.