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Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin‐receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin‐deficient mice show increased DA activity in reward‐related brain regions. The objective of this study was to examine whether basal D2R‐binding differences...
We investigated D1, D2 receptors and dopamine transporter (DAT) binding levels in mice lacking all three opioid receptors and wild‐type (WT) mice on three different genetic backgrounds. Quantitative autoradiography was used to determine the level of radioligand binding to the D1 and D2 receptors and DAT labeled with [3H]SCH23390, [3H]raclopride, and [3H]mazindol, respectively in triple‐opioid receptor...
Several lines of evidence implicate aberrant glutamate neurotransmission in the pathophysiology of schizophrenia. In particular, compromised signaling through the N‐methyl‐D‐aspartate (NMDA) receptor has been linked to positive, negative, and cognitive symptoms of this illness. Studies in postmortem brain have identified altered expression of several structural and signaling molecules of the postsynaptic...
The need for positron emission tomography (PET)‐radioligands that are sensitive to changes in endogenous serotonin (5‐HT) levels in brain is recognized in experimental and clinical psychiatric research. We recently developed the novel PET radioligand [11C]AZ10419369 that is highly selective for the 5‐HT1B receptor. In this PET‐study in three cynomolgus monkeys, we examined the sensitivity of [11C]AZ10419369...
Epidemiological studies have revealed a strong genetic contribution to the risk for depression. Both reduced hippocampal serotonin neurotransmission and brain‐derived neurotrophic factor (BDNF) levels have been associated with increased depression vulnerability and are also regulated during aging. Brains from young (5 months old) and old (13 months old) congenital Learned Helplessness rats (cLH),...
The importance of the BAR domain of endophilin in synaptic vesicle endocytosis was tested in presynaptic microinjection experiments in the lamprey giant synapse. Antibodies as well as Fab fragments directed to the BAR domain caused a stimulus‐dependent decrease in the number of synaptic vesicles along with an accumulation of shallow clathrin coated pits in the periactive zone. Moreover, the isolated...
We verified the hypothesis that serotonin (5‐HT)2 receptors control the locomotor effects of nicotine (0.4 mg kg−1) in rats by using the 5‐HT2A receptor antagonist M100907, the preferential 5‐HT2A receptor agonist DOI, the 5‐HT2C receptor antagonist SB 242084, and the 5‐HT2C receptor agonists Ro 60‐0175 and WAY 163909. Repeated pairings of a test environment with nicotine for 5 days, on Day 10 significantly...
In the hippocampus, glucocorticoids bind to two types of receptors: the mineralocorticoid receptor, which binds corticosterone with high affinity and is tonically occupied; and the glucocorticoid receptor, which is occupied during stress and at certain phases in the circadian cycle. Diabetes mellitus increases levels of glucocorticoids in both humans and animal models. To explore the contributions...
The type‐1 glycine transporter (GlyT1) is an important target for the development of new medications for schizophrenia. A specific and selective positron emission tomography (PET) GlyT1 ligand would facilitate drug development studies to determine whether a drug reaches this target and help establish suitable doses for clinical trials. This article describes the evaluation of three candidate GlyT1...
Our laboratory has recently demonstrated altered expression of phosphodiesterase (PDE) 4A and 4B in subjects with autism, bipolar disorder, and schizophrenia, suggesting disrupted cAMP signaling in these diagnostic groups. In the current study, we measured expression of PDEs in rat frontal cortex (FC) following chronic treatment with clozapine, fluoxetine, haloperidol, lithium, olanzapine, valproic...
Short‐acting dopamine (DA) agonists are usually administered several times a day resulting in fluctuating plasma and brain levels. DA agonists providing continuous dopaminergic stimulation may achieve higher therapeutic benefit for example by alleviating nocturnal disturbances as well as early morning akinesia. In the present study continuous release (CR) of pramipexole (PPX) was maintained by subcutaneous...
Cognitive and motor deficits are pervasive in children that suffer early brain injury. The aim of this study was to determine the impact that early damage has on dendritic spine density and other aspects of dendritic morphology of neurons in the motor cortex. Also of interest was how changes in dendritic structure evolved across the lifespan. Ischemia was induced in 10‐day‐old Long Evans rats by injection...
There is an expanding body of work characterizing dopaminergic modulation of synaptic plasticity in the hippocampus CA1 region, an area known to be involved in learning and memory. However, in vitro studies to date have focused almost exclusively on the proximal and distal apical dendritic layers (strata radiatum and lacunosum moleculare, respectively). In this report, we establish that dopaminergic...
Aim. To test for α2 adrenergic modulation of dopamine D2/3 receptor availability in striatum of living mice using the high‐affinity ligand [18F]fallypride and microPET. Methods. Groups of anesthetized mice were pretreated with saline, the α2‐agonist clonidine (1 mg/kg), and the α2‐antagonists RX821002 (1 mg/kg) and yohimbine (1 mg/kg). Dynamic microPET recordings lasting 120 min were then initiated...
Objectives:The endocannabinoid system is an important modulatory system in the brain. Complex interactions with brain dopaminergic circuits have been demonstrated. The aim of this study was to investigate the in vivo effect of the commonly used antiparkinsonian drugs, levodopa (L‐DOPA) and bromocriptine, on type 1 cannabinoid (CB1) receptors, using the PET radioligand [18F]MK‐9470.
Experimental approach:Seventeen...
Dopamine D3 receptors have the highest dopamine affinity of all dopamine receptors, and may thereby regulate dopamine signaling mediated by volume transmission. Changes in D3 receptor isoform expression may alter D3 receptor function, however, little is known regarding coordination of D3 isoform expression in response to perturbations in dopaminergic stimulation. To determine the effects of dopamine...
Positron emission tomography (PET) antagonist ligands such as [11C]‐raclopride are commonly used to study dopamine D2 receptor (D2) binding of antipsychotics. It has been suggested that agonist radioligands bind preferentially to the high‐affinity state of D2 receptor and may provide a more relevant means of assessing D2 occupancy. The main objective of this study was to determine if D2 receptor occupancy...
Recent research has suggested that epigenetic mechanisms, which exert lasting control over gene expression without altering the genetic code, could mediate stable changes in brain function. A growing body of evidence supports the idea that epigenetic changes play a role in the etiology of aging and its associated brain dysfunction. The present study was undertaken to evaluate the age‐related changes...
In vitro experiments have shown that protoporphyrin IX (PPIX) binds to the translocator protein 18 kDa (TSPO), which transports cholesterol across the outer mitochondrial membrane. The purpose of this study was to examine whether binding of PPIX to TSPO can also be detected in vivo using positron emission tomography and [11C]PBR28, a radioligand that binds with high affinity and selectivity to TSPO...