Evaluating In-home Assistive Technology for Dementia Caregivers.

Objectives: Dementia caregivers (CGs) are at heightened risk for developing problems with anxiety and depression. Much attention has been directed toward developing and deploying interventions designed to protect CG health, but few have been supported by rigorous empirical evidence. Technology-based interventions that are effective, scalable, and do not add greatly to the CG burden are of particular interest.

Randomized clinical study of safety, pharmacokinetics, and pharmacodynamics of RIPK1 inhibitor GSK2982772 in healthy volunteers.

GSK2982772 is a highly selective inhibitor of receptor-interacting protein kinase 1 (RIPK1) being developed to treat chronic inflammatory diseases. This first-in-human study evaluated safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) of GSK2982772 administered orally to healthy male volunteers. This was a Phase I, randomized, placebo-controlled, double-blind study.

Dopamine D2 Receptor Signaling in the Nucleus Accumbens Comprises a Metabolic-Cognitive Brain Interface Regulating Metabolic Components of Glucose Reinforcement.

Appetitive drive is influenced by coordinated interactions between brain circuits that regulate reinforcement and homeostatic signals that control metabolism. Glucose modulates striatal dopamine (DA) and regulates appetitive drive and reinforcement learning. Striatal DA D2 receptors (D2Rs) also regulate reinforcement learning and are implicated in glucose-related metabolic disorders.

Bromocriptine administration reduces hyperphagia and adiposity and differentially affects dopamine D2 receptor and transporter binding in leptin-receptor-deficient Zucker rats and rats with diet-induced obesity.

Background: The dopamine (DA) D(2) receptor (D2R) agonist bromocriptine (BC) decreases body fat in animal and human models and increases lean muscle mass, improves glucose intolerance and insulin resistance, and reduces triglycerides and free fatty acids. We have previously shown a negative correlation between D2R and body weight in obese individuals and in rodents, and that chronic food restriction increases D2R binding in genetically obese rats. The purpose of this study was to assess whether the antiobesity and metabolic effects of BC are related to changes in midbrain DA and D2R activity by measuring D2R and DA transporter (DAT) binding in a genetic (leptin-receptor-deficient) and environmental (diet-induced) rodent obesity model.

The effects of cocaine on regional brain glucose metabolism is attenuated in dopamine transporter knockout mice.

Cocaine's ability to block the dopamine transporter (DAT) is crucial for its reinforcing effects. However the brain functional consequences of DAT blockade by cocaine are less clear since they are confounded by its concomitant blockade of norepinephrineand serotonin transporters. To separate the dopaminergic from the non-dopaminergic effects of cocaine on brain function we compared the regional brain metabolic responses to cocaine between dopamine transporter deficient (DAT(-/-)) mice with that of their DAT(+/+) littermates.

Effects of chronic oral methylphenidate on cocaine self-administration and striatal dopamine D2 receptors in rodents.

Background: Methylphenidate (MP) and amphetamine, which are the mainstay for the treatment of ADHD, have raised concerns because of their reinforcing effects and the fear that their chronic use during childhood or adolescence could induce changes in the brain that could facilitate drug abuse in adulthood.

Methods: Here we measured the effects of chronic treatment (8 months) with oral MP (1 or 2 mg/kg), which was initiated in periadolescent rats (postnatal day 30). Following this treatment, rats were tested on cocaine self-administration.

Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking.

Dopamine (DA) signals are transmitted via specific receptors including the D2 receptors (D2R). Previous studies have shown that D2R upregulation in the nucleus accumbens (NAc) attenuated alcohol consumption. We hypothesized that upregulation of D2R in the NAc would significantly influence alcohol drinking.

Comparison of Brain Glucose Metabolism and Monoamine Oxidase B (MAO B) in Traumatic Brain Injury.

OBJECTIVE: Positron emission tomography (PET) studies in patients with temporal lobe epilepsy have reported that hypometabolism in temporal regions is associated with elevated monoamine oxidase B (MAO B) probably reflecting gliosis. The purpose of this study was to examine a group of head trauma patients suffering from seizures and memory loss to determine whether hypometabolic regions show correspondingly elevated MAO B.METHODS: Seven patients with traumatic brain injury received PET scans with (18)FDG and [(11)C]L-deprenyl-D2 to measure regional glucose metabolism (LCMRglu) and MAO B respectively.

PET Studies of the Effect of the Antidepressant Drugs Nefazodone or Paroxetine on [11C]Raclopride Binding in Human Brain.

Serotonin modulates dopamine release in the striatum. In this study we set out to determine whether nefazodone and paroxetine, two antidepressant drugs that interact with the brain serotonin system, produce detectable changes in synaptic dopamine in vivo in the human brain using positron emission tomography (PET) and [11C]raclopride, a dopamine D-2 receptor specific radiotracer that is sensitive to changes in synaptic dopamine. Three normal healthy human volunteers had 4 PET/[11C]raclopride scans each in 2 sessions.

Role of dopamine in the therapeutic and reinforcing effects of methylphenidate in humans: results from imaging studies.

Methylphenidate is the most commonly prescribed drug for the treatment of ADHD. We have used positron emission tomography to assess the role that methylphenidate's effects in brain dopamine have on its therapeutic and reinforcing effects. We have documented that in the human brain therapeutic doses of methylphenidate block more than 50% of the dopamine transporters and significantly enhance extracellular DA, an effect that appears to be modulated by the rate of DA release.

Changes in brain functional homogeneity in subjects with Alzheimer's disease.

Imaging studies have reported marked reductions in brain glucose metabolism in Alzheimer's Disease (AD). However, less is known about disruptions in the patterns of brain metabolic activity. Here we questioned whether AD affects the patterns of homogeneity/heterogeneity in brain metabolism.