Non-destructive comparative evaluation of fossil amber using terahertz time-domain spectroscopy.

Fossilized plant resins, or ambers, offer a unique paleontological window into the history of life. A natural polymer, amber can preserve aspects of ancient environments, including whole organisms, for tens or even hundreds of millions of years. While most amber research involves imaging with visual light, other spectra are increasingly used to characterize both organismal inclusions as well as amber matrix.

Metabolic studies of synaptamide in an immortalized dopaminergic cell line.

Introduction: Synaptamide, the N-acylethanolamine of docosahexaenoic acid (DHA), is structurally similar to the endocannabinoid N-arachidonoylethanolamine, anandamide. It is an endogenous ligand at the orphan G-protein coupled receptor 110 (GPR110; ADGRF1), and induces neuritogenesis and synaptogenesis in hippocampal and cortical neurons, as well as neuronal differentiation in neural stem cells.

Purpose: Our goal was to characterize the metabolic fate (synthesis and metabolism) of synaptamide in a dopaminergic cell line using immortalized fetal mesencephalic cells (N27 cells).

N-Docosahexaenoylethanolamine (synaptamide): Carbon-14 radiolabeling and metabolic studies.

N-Docosahexaenoylethanolamine (synaptamide) is structurally similar to the endocannabinoid N-arachidonoylethanolamine (anandamide), but incorporates the omega-3 22:6 fatty acid docosahexaenoic acid (DHA) in place of the omega-6 20:4 fatty acid arachidonic acid (AA). Some brain membrane lipid effects may be mediated via synaptamide. In competition experiments with mouse brain homogenate in vitro, we found that synaptamide was an order-of-magnitude poorer inhibitor of radioactive anandamide hydrolysis than was anandamide itself.

Brain uptake and metabolism of the endocannabinoid anandamide labeled in either the arachidonoyl or ethanolamine moiety.

Introduction: Anandamide (N-arachidonoylethanolamine) is a retrograde neuromodulator that activates cannabinoid receptors. The concentration of anandamide in the brain is controlled by fatty acid amide hydrolase (FAAH), which has been the focus of recent drug discovery efforts. Previous studies in C57BL/6 mice using [H-arachidonoyl]anandamide demonstrated deposition of tritium in thalamus and cortical areas that was blocked by treatment with an FAAH inhibitor and that was not seen in FAAH-knockout mice.

Integrity of (111)In-radiolabeled superparamagnetic iron oxide nanoparticles in the mouse.

Introduction: Iron-oxide nanoparticles can act as contrast agents in magnetic resonance imaging (MRI), while radiolabeling the same platform with nuclear medicine isotopes allows imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), modalities that offer better quantification. For successful translation of these multifunctional imaging platforms to clinical use, it is imperative to evaluate the degree to which the association between radioactive label and iron oxide core remains intact in vivo.

Methods: We prepared iron oxide nanoparticles stabilized by oleic acid and phospholipids which were further radiolabeled with (59)Fe, (14)C-oleic acid, and (111)In.

Long-term effects of irradiation with iron-56 particles on the nigrostriatal dopamine system.

Exposure to heavy ions during a Mars mission might damage the brain, thus compromising mission success and the quality of life of returning astronauts. Several workers have suggested that the dopamine system is particularly sensitive to heavy ion radiation, but direct evidence for this notion is lacking. We examined measures of brain dopamine viability at times up to 15 months after acute exposure of rats to (56)Fe (1.

MicroPET investigation of chronic long-term neurotoxicity from heavy ion irradiation.

Positron emission tomography (PET) permits imaging of the regional biodistribution and pharmacokinetics of compounds labeled with short-lived positron-emitting isotopes. It has enabled evaluation of neurochemical systems in the living human brain, including effects of toxic substances. MicroPET devices allow studies of the rat brain with a spatial resolution of approximately 2 mm.

Evidence that methylphenidate enhances the saliency of a mathematical task by increasing dopamine in the human brain.

Objective: Methylphenidate is the most commonly prescribed drug for attention deficit hyperactivity disorder (ADHD), yet its therapeutic mechanisms are poorly understood. The objective of this study was to assess if methylphenidate, by increasing dopamine (neurotransmitter involved in motivation) in brain, would enhance the saliency of an academic task, making it more interesting.

Method: Healthy subjects (N=16) underwent positron emission tomography with [(11)C]raclopride (dopamine D(2) receptor radioligand that competes with endogenous dopamine for binding) to assess the effects of oral methylphenidate (20 mg) on extracellular dopamine in the striatum.

Effects of alcohol detoxification on dopamine D2 receptors in alcoholics: a preliminary study.

Imaging studies in patients with Type II alcohol dependence have revealed significant reductions in dopamine (DA) D2 receptor availability. Here we assessed the effects of alcohol detoxification in DA D2 receptors in alcoholic subjects. We evaluated 14 patients with Type II alcohol dependence tested within 6 weeks of detoxification and then re-tested 1-4 months later while alcohol free.

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.

Brain DA D2 receptors predict reinforcing effects of stimulants in humans: replication study.

We had shown that striatal DA D2 receptors levels predicted the reinforcing responses to the psychostimulant drug methylphenidate in nondrug-abusing subjects. Here, we assessed the replicability of this finding. We measured D2 receptors with PET and [(11)C]raclopride (twice to determine stability) in seven nondrug-abusing subjects to assess if they predicted the self-reports of "drug-liking" to intravenous methylphenidate (0.

"Nonhedonic" food motivation in humans involves dopamine in the dorsal striatum and methylphenidate amplifies this effect.

The drive for food is one of the most powerful of human and animal behaviors. Dopamine, a neurotransmitter involved with motivation and reward, its believed to regulate food intake in laboratory animals by modulating its rewarding effects through the nucleus accumbens (NA). Here we assess the involvement of dopamine in "nonhedonic" food motivation in humans.

Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications.

Methylphenidate (Ritalin) is an effective drug in the treatment of attention deficit hyperactivity disorder. However, the doses required therapeutically vary significantly between subjects and it is not understood what determines these differences. Since methylphenidate's therapeutic effects are in part due to increases in extracellular DA secondary to blockade of dopamine transporters (DAT), the variability could reflect differences in levels of DAT blockade.