Fallypride

Abstract: While methamphetamine addiction has been associated with both impulsivity and striatal dopamine D(2)/D(3) receptor deficits, human studies have not directly linked the latter two entities. We therefore compared methamphetamine-dependent and healthy control subjects using the Barratt Impulsiveness Scale (version 11, BIS-11) and positron emission tomography with [(18)F]fallypride to measure striatal dopamine D(2)/D(3) receptor availability. The methamphetamine-dependent subjects reported recent use of the drug 3.3 g per week, and a history of using methamphetamine, on average, for 12.5 years. They had higher scores than healthy control subjects on all BIS-11 impulsiveness subscales (p < 0.001). Volume-of-interest analysis found lower striatal D(2)/D(3) receptor availability in methamphetamine-dependent than in healthy control subjects (p < 0.01) and a negative relationship between impulsiveness and striatal D(2)/D(3) receptor availability in the caudate nucleus and nucleus accumbens that reached statistical significance in methamphetamine-dependent subjects. Combining data from both groups, voxelwise analysis indicated that impulsiveness was related to D(2)/D(3) receptor availability in left caudate nucleus and right lateral putamen/claustrum (p < 0.05, determined by threshold-free cluster enhancement). In separate group analyses, correlations involving the head and body of the caudate and the putamen of methamphetamine-dependent subjects and the lateral putamen/claustrum of control subjects were observed at a weaker threshold (p < 0.12 corrected). The findings suggest that low striatal D(2)/D(3) receptor availability may mediate impulsive temperament and thereby influence addiction.

Abstract: We have previously demonstrated changes in dopaminergic neurotransmission after intensive exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD), including an increase in the dopamine D2 receptor (DA-D2R), using noninvasive PET imaging with the radioligand [18F]fallypride. The purpose of this feasibility and translational study was to examine whether intensive exercise leads to similar alterations in DA-D2R expression using PET imaging with [18F]fallypride in individuals with early-stage PD. In this pilot study, four patients with early-stage PD were randomized to receive intensive exercise (treadmill training sessions three times/week for 8 weeks) or no exercise. Two healthy age-matched individuals participated in treadmill training. Alterations in the DA-D2R binding potential (BP) as a marker for receptor expression were determined using PET imaging with [18F]fallypride. Turning performance in the patients with PD as a measure of postural control and the Unified Parkinson's Disease Rating Scale scores pre-exercise and postexercise were determined. Our data showed an exercise-induced increase in [18F]fallypride BP as well as improved postural control in patients with PD who exercised. Changes in DA-D2R BP were not observed in patients with PD who did not exercise. These results suggest that exercise can lead to neuroplasticity in dopaminergic signaling and contribute to improved function that may be task specific (postural control) in early-stage PD.

Abstract: Objective: All drugs of abuse induce a phasic dopamine release within the striatum that does not undergo habituation. Prolonged substance consumption impairs the natural function of the mesolimbic dopamine system, as shown by a decrease in the availability of striatal dopamine 2 (D 2 ) receptors in patients suffering from cocaine, heroin, amphetamine, and alcohol dependence. However, it is unclear whether similar changes can also be observed in heavy-smoking nicotine-dependent smokers. Method: In vivo D 2 /D 3 receptor availability was determined with [ 18 F]fallypride positron emission tomography in 17 heavy-smoking nicotine-dependent subjects and in 21 age-matched never-smoking comparison subjects. The smokers were scanned twice: first, during a period of usual consumption and second, 24 hours after smoking cessation. Results: Independent of the withdrawal status, the nicotine-dependent smokers displayed significantly less availability of D 2 /D 3 receptors within the bilateral putamen functionally cove...

Abstract: The purpose of the current study was to examine changes in dopamine D2 receptor (DA-D2R) expression within the basal ganglia of MPTP mice subjected to intensive treadmill exercise. Using Western immunoblotting analysis of synapto- neurosomes and in vivo positron emission tomography (PET) imaging employing the DA-D2R specific ligand ( 18 F)fallypride, we found that high intensity treadmill exercise led to an increase in striatal DA-D2R expression that was most pronounced in MPTP compared to saline treated mice. Exercise-induced changes in the DA-D2R in the dopamine-depleted basal ganglia are consistent with the potential role of this receptor in modulat- ing medium spiny neurons (MSNs) function and behavioral recovery. Importantly, findings from this study support the ra- tionale for using PET imaging with ( 18 F)fallypride to examine DA-D2R changes in individuals with Parkinson's Disease (PD) undergoing high-intensity treadmill training. 2010 Move- ment Disorder Society