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In a recent PET study, we demonstrated the ability to measure amphetamine‐induced DA release in the human cortex with the relatively high affinity dopamine D2/3 radioligand [11C]FLB 457 (Narendran et al., [2009] Synapse 63:447–461). The aim of this study was to evaluate the reproducibility and reliability of [11C]FLB 457 in the same imaging paradigm we used to measure amphetamine‐induced DA transmission...
Prenatal cocaine exposure induces cytoarchitectural changes in the embryonic neocortex; however, the biological mechanisms and type of cortical neurons involved in these changes are not known. Previously, we found that neural progenitor proliferation in the neocortical ventricular zone (VZ) is inhibited by cocaine; here, we examine the changes in cortical neurogenesis and migration of glutamate and...
Changes in α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptor (AMPAR) surface expression in the rodent nucleus accumbens (NAc) are produced by cocaine exposure and implicated in addiction‐related behaviors. The direction of change depends on the animal's prior drug history. However, little is known about the effect of a single exposure to cocaine on AMPAR distribution in the NAc of untreated...
Microtubules are involved in the formation of axons and dendrites, maintenance of neuronal morphology, and cellular trafficking. Recent studies suggest that drugs affecting dopamine activity in the brain can induce cytoskeletal modifications. For instance, we have demonstrated in acute rat brain slices a molecular chain of events connecting dopamine D1 receptor to aberrant phosphorylation of the microtubule‐associated...
Activation of the corticotropin‐releasing factor‐1 (CRF‐1) receptor in the anterolateral BNST (BSTal), a key subdivision of the extended amygdala, elicits opiate‐seeking behavior exacerbated by stress. However, it is unknown whether the presence of CRF‐1 affects expression of the μ‐opioid receptor (μ‐OR) in the many GABAergic BSTal neurons implicated in the stress response. We hypothesized that deletion...
We previously reported the absence of high‐affinity binding of the group II metabotropic glutamate receptor agonists LY 354,740 and LY 379,268 to the D2L dopamine receptor. A rebuttal to our findings has since been reported (see Introduction section); this study represents our response. Analysis by LCMS of LY 354,740 and LY 379,268 used in this study revealed the correct molecular mass for these compounds...
CART (Cocaine‐ and amphetamine‐regulated transcript) peptide has been implicated in playing a modulatory role in reward and reinforcement. Previously, our laboratory demonstrated that injections of CART peptide (CART 55‐102) into the nucleus accumbens (NAc) attenuated both cocaine‐ and dopamine‐induced increases in locomotor activity (LMA), and attenuated cocaine reward as well. In this study, the...
It has been reported that stress and facilitation of dopamine neuronal system are closely related. In the present study, the effects of stress on the binding of antagonist‐based [11C]raclopride and agonist‐based (R)‐2‐CH3O‐N‐n‐ propylnorapomorphine ([11C]MNPA) to D2/D3 receptors were evaluated in the striatum of conscious monkey brain. The stress state assessed from plasma cortisol level was negatively...
Synapses represent specialized cell–cell contact sites between nerve cells. These structures mediate the rapid and efficient transmission of signals between neurons and are surrounded by glial cells. Previous investigations have shown that astrocytes are important for the formation, maintenance, and function of CNS synapses. To study effects of glial‐derived molecules on synaptogenesis, we have established...
We have recently clarified that nicotinic acetylcholine receptors (nAChRs) expressed in the thalamus play an important role in antiallodynic effects produced by the nAChR agonist, 5‐iodo‐3‐(2(S)‐azetidinylmethoxy)pyridine (5IA). This study aimed to reveal the in vivo relationship between thalamic nAChR occupancy rates and antiallodynic effects using 5IA and [125I]5IA. We partially ligated the sciatic...
This project was done in order to determine why the annual incidence of metoclopramide‐associated tardive dyskinesia is much higher than that for the commonly used antipsychotics. To test the hypothesis that metoclopramide tardive dyskinesia may be associated with high concentrations of metoclopramide in the substantia nigra under clinical conditions, the nonspecific binding of tritiated antipsychotics...
Spontaneous and antagonist‐precipitated withdrawal from nicotine is characterized by marked deficits in extracellular dopamine (DA) in striatum, especially in nucleus accumbens, that have been thought to underlie the affective state associated with drug discontinuation. Uptake via the dopamine transporter (DAT) is a key mechanism for regulating the concentrations of extracellular DA. Accordingly,...
Ketamine exerts powerful anesthetic, psychotic, and antidepressant effects in both healthy volunteers and clinically depressed patients. Although ketamine targets particular glutamate receptors, there is a dearth of evidence for additional, alternative molecular substrates for the behavioral actions of this N‐methyl‐D‐aspartate (NMDA) receptor antagonist drug. Here, we provide behavioral and molecular...
Agmatine, a metabolite of L‐arginine, is considered as a novel putative neurotransmitter. It has been detected in axon terminals that synapse with pyramidal cells in the hippocampus, a brain region that is critically involved in spatial learning and memory. However, the role of agmatine in learning and memory is poorly understood. Recently, we demonstrated water maze training‐induced increases in...
Endocannabinoids, anandamide, and 2‐arachidonoyl glycerol are involved in food intake and appetite. Although anandamide is now thought to be a ligand for vanilloid receptor, receptors that are targets of anandamide could play a similar role in eating behaviors and related disorders. This study therefore focused on the receptor, which is called G‐protein‐coupled receptor 55 (GPR55) that had recently...
Purpose: Attention‐deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) are highly comorbid and may share a genetic vulnerability. Methylphenidate (MPH), a dopamine transporter (DAT) blocker, is an effective drug for most ADHD patients. Although dopamine D4 receptor (DRD4) and dopamine transporter (DAT1) genes have a role in both disorders, little is known about how these genes...
The purpose of this study was to examine sex differences in the correlations of d‐amphetamine (d‐AMPH) induced displacements of [18F]fallypride in striatal and extrastriatal regions in relation to affect and cognition. Seven male and six female healthy subjects, whose mean age was 25.9 years, underwent positron emission tomography (PET) with [18F]fallypride at baseline and 3 h after a 0.43 mg/kg oral...
The nucleus accumbens (NAc) is a limbic structure in the forebrain that plays a critical role in cognitive function and addiction. Dopamine modulates activity of medium spiny neurons (MSNs) in the NAc. Both dopamine D1‐like and D2‐like receptors (including D1R or D1,5R and D2R or D2,3,4R, respectively) are thought to play critical roles in cocaine addiction. Our previous studies demonstrated that...
Depletion of central serotonin (5‐HT) levels and dysfunction in serotonergic transmission are implicated in a variety of human CNS disorders. The mechanisms behind these serotonergic deficits have been widely studied using rodent models, but only to a limited extent in larger animal models. The pig is increasingly used as an experimental animal model especially in neuroscience research. Here, we present...
Two moderately lipophilic, high affinity ligands for metabotropic glutamate receptor subtype 1 (mGluR1) were radiolabeled with a positron‐emitting radioisotope and evaluated in rhesus monkey as potential PET tracers. Both ligands were radiolabeled with fluorine‐18 via nucleophilic displacement of the corresponding 2‐chloropyridine precursor with [18F]potassium fluoride. [18F]MK‐1312 was found to have...
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