Abstract:
:Relapse to cocaine dependence, even after extended abstinence, involves a number of liability factors including impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) and cue reactivity (sensitivity to cues associated with cocaine-taking which can promote cocaine-seeking). These factors have been mechanistically linked to serotonin (5-hydroxytryptamine, 5-HT) signaling through the 5-HT(2A) receptor (5-HT(2A)R) and 5-HT(2C)R; either a selective 5-HT(2A)R antagonist or a 5-HT(2C)R agonist suppresses impulsivity and cocaine-seeking in preclinical models. We conducted proof-of-concept analyses to evaluate whether a combination of 5-HT(2A)R antagonist plus 5-HT(2C)R agonist would have synergistic effects over these liability factors for relapse as measured in a 1-choice serial reaction time task and cocaine self-administration/reinstatement assay. Combined administration of a dose of the selective 5-HT(2A)R antagonist M100907 plus the 5-HT(2C)R agonist WAY163909, each ineffective alone, synergistically suppressed cocaine-induced hyperactivity, inherent and cocaine-evoked impulsive action, as well as cue- and cocaine-primed reinstatement of cocaine-seeking behavior. The identification of synergism between a 5-HT(2A)R antagonist plus a 5-HT(2C)R agonist to attenuate these factors important in relapse indicates the promise of a bifunctional ligand as an anti-addiction pharmacotherapeutic, setting the stage to develop new ligands with improved efficacy, potency, selectivity, and in vivo profiles over the individual molecules.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Cunningham KA,Anastasio NC,Fox RG,Stutz SJ,Bubar MJ,Swinford SE,Watson CS,Gilbertson SR,Rice KC,Rosenzweig-Lipson S,Moeller FGdoi
10.1021/cn300072usubject
Has Abstractpub_date
2013-01-16 00:00:00pages
110-21issue
1issn
1948-7193journal_volume
4pub_type
杂志文章abstract::Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding th...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn500049n
更新日期:2014-05-21 00:00:00
abstract::Online electrochemical detection techniques are the state-of-the-art for evaluating chemical communication in the brain underlying motivated behavior and decision making. In this Viewpoint, we discuss avenues for future technological development, as well as the requirement for increasingly sophisticated and interdisci...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/cn500322y
更新日期:2015-01-21 00:00:00
abstract::Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha-synuclein (α-syn) fibrillization in vitro. As a first step toward developing molecules from this scaffold as positron emission tomography imaging agents, we were interested in evaluating their blood-...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00236
更新日期:2018-11-21 00:00:00
abstract::Peripheral immunity is thought to be dysregulated in Parkinson's disease (PD) and may provide an avenue for novel immunotherapeutic interventions. Gut microbiota is a potential factor for modulating immunotherapy response. Considering the possibly complex role of the gut-brain axis in PD, we used a preclinical model t...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00386
更新日期:2020-10-21 00:00:00
abstract::Manganese (Mn) may foster aggregation of alpha-synuclein (αSyn) contributing to the pathogenesis of PD. Here, we examined the influence of αSyn overexpression on distribution and oxidation states of Mn in frozen-hydrated primary midbrain neurons (PMNs) by synchrotron-based X-ray fluorescence (XRF) and X-ray absorption...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.5b00093
更新日期:2015-10-21 00:00:00
abstract::Natural environments contain numerous volatile compounds emanating from a large number of sources, and the survival of many animals depends on their ability to segregate odors of interest within complex odorous scenes. In a recent paper, we described how the ability of mice to detect odors within mixtures depends on t...
journal_title:ACS chemical neuroscience
pub_type: 评论,杂志文章
doi:10.1021/cn500199n
更新日期:2014-10-15 00:00:00
abstract::Calcitonin gene-related peptide (α-CGRP) released from perivascular sensory nerves induces decreases in diastolic blood pressure (DBP). Experimentally, this can be shown by spinal thoracic (T9-T12) electrical stimulation of these afferent fibers. Because ergotamine inhibits these neurogenic vascular responses and disp...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00611
更新日期:2019-07-17 00:00:00
abstract::Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) autophosphorylation at Thr286 and Thr305/Thr306 regulates kinase activity and modulates subcellular targeting and is critical for normal synaptic plasticity and learning and memory. Here, a mass spectrometry-based approach was used to identify Ca(2+)-dependent a...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn500337u
更新日期:2015-04-15 00:00:00
abstract::Neurotensin (NT) exerts its analgesic effects through activation of the G protein-coupled receptors NTS1 and NTS2. This opioid-independent antinociception represents a potential alternative for pain management. While activation of NTS1 also induces a drop in blood pressure and body temperature, NTS2 appears to be an a...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.9b00390
更新日期:2019-11-20 00:00:00
abstract::Protein function depends on both protein structure and amino acid (aa) sequence. Here we show that modular features of both structure and function can be quantified economically from the aa sequences alone for the small (40,42 aa) plaque-forming (aggregative) amyloid beta fragments. Some edge and center features of th...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn5001793
更新日期:2015-05-20 00:00:00
abstract::The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer's disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer'...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00014
更新日期:2017-07-19 00:00:00
abstract::Reversion of protein or peptide aggregation is a formidable task, important in various domains of research at the interface of chemistry, medicine, and nanoscience. A novel class of dipeptides, termed as β-breaker dipeptides (BBDPs), is identified, which can be incorporated into the self-recognizing sequences to gener...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn500064z
更新日期:2014-05-21 00:00:00
abstract::Several antidepressants increase adult hippocampal neurogenesis (ahNG) in rodents, primates, and, potentially, humans. This effect may at least partially account for their therapeutic activity. The availability of antidepressants whose mechanism of action involves different neurotransmitter receptors represents an opp...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00175
更新日期:2017-09-20 00:00:00
abstract::Neuroinflammatory processes promote a constellation of neurochemical and hormonal changes resulting in profound effects on motivational states (anhedonia), mood (depression and anxiety disorders), and cognitive function (decrements in learning and memory). The enhancement of immunoregulatory processes, such as increas...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.8b00386
更新日期:2019-01-16 00:00:00
abstract::A new generation of ligands designed to interact with the α-helix/β-strand discordant region of the amyloid-β peptide (Aβ) and to counteract its oligomerization is presented. These ligands are designed to interact with and stabilize the Aβ central helix (residues 13-26) in an α-helical conformation with increased inte...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00485
更新日期:2019-03-20 00:00:00
abstract::The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1-5. In this article, w...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn100093f
更新日期:2011-02-16 00:00:00
abstract::Recent clinical approvals of brain imaging radiotracers targeting amyloid-β provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diag...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.9b00093
更新日期:2019-06-19 00:00:00
abstract::Opium is the latex from the opium poppy Papaver somniferum L., which humankind has utilized since ancient Mesopotamia all the way to modern times. Opium used to be surrounded in divine mystery or magic-like abilities and was given to cure a wide variety of diseases until its analgesic, antitussive, and antidiarrheal p...
journal_title:ACS chemical neuroscience
pub_type: 历史文章,杂志文章,评审
doi:10.1021/acschemneuro.8b00459
更新日期:2018-10-17 00:00:00
abstract::No selective drugs exist, and we have been designing, synthesizing, and evaluating multitarget-directed ligands since the beginning of modern medicinal chemistry, without knowing it, most possibly. The challenge to discover the efficient Multi-Target Small Molecules (MTSMs) for Alzheimer's disease (AD) therapy implies...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.8b00069
更新日期:2018-03-21 00:00:00
abstract::The nicotinic acetylcholine receptor (nAChR) family, the archetype member of the pentameric ligand-gated ion channels, is ubiquitously distributed in the central and peripheral nervous systems, and its members are the targets for both genetic and acquired forms of neurological disorders. In the central nervous system,...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.9b00041
更新日期:2019-05-15 00:00:00
abstract::The amyloid beta (Aβ) fibrillar aggregate is the hallmark of Alzheimer's disease (AD). Disassembling preformed fibril or inhibiting Aβ aggregation is considered as a therapeutic strategy for AD. Increasing evidence shows that green tea extracts, epigallocatechin-3-gallate (EGCG, containing an extra gallic acid ester g...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00277
更新日期:2020-06-17 00:00:00
abstract::Baicalein, a flavonoid derived from the roots of Scutellariae baicalensis Georgi, has shown health benefits for an array of human diseases including dementia. The senescence-accelerated mouse prone 8 (SAMP8) strain is extensively used as a senile dementia model. To further investigate the effects of baicalein in SAMP8...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00074
更新日期:2018-07-18 00:00:00
abstract::The fibrillogenesis of amyloid-β protein (Aβ) is considered a crucial factor in the pathogenesis of Alzheimer's disease (AD). Hence, inhibiting Aβ fibrillogenesis is regarded as the primary therapeutic strategy for the prevention and treatment of AD. However, the development of effective inhibitors against Aβ fibrillo...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00441
更新日期:2019-01-16 00:00:00
abstract::Brain-eating amoebae (Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri) can cause opportunistic infections involving the central nervous system. It is troubling that the mortality rate is more than 90% despite advances in antimicrobial chemotherapy over the last few decades. Here, we describe urgent k...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00343
更新日期:2017-11-15 00:00:00
abstract::Amyloid fibrils are the most distinct components of the plaques associated with various neurodegenerative diseases. Kinetic studies of amyloid fibril formation shed light on the microscopic mechanisms that underlie this process as well as the contributions of internal and external factors to the interplay between diff...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.5b00104
更新日期:2015-08-19 00:00:00
abstract::Chondroitin sulfate proteoglycans (CSPGs) are the most abundant components of glial scar formed after severe traumatic brain injury as well as spinal cord injury and play a crucial inhibitory role in axonal regeneration by selective contraction of filopodia of the growth cone of sprouting neurites. Healing of central ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00004
更新日期:2020-02-05 00:00:00
abstract::Previous work has established that D-serine (D-Ser) plays important roles in certain neurological processes. Study on its uptake/storage and release by neuronal cells is highly significant for elucidating relevant mechanisms. In this work, PC-12 cells were incubated with racemic Ser (100 μM each enantiomer). After inc...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn5003122
更新日期:2015-04-15 00:00:00
abstract::Biology has inspired solutions to many engineering problems, including chemical sensing. Modern approaches to chemical sensing have been based on the biological principle of combining cross-selective chemical sensors with a pattern recognition engine to identify odors. Here, we review some recent advances made in mimi...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn200027r
更新日期:2011-05-27 00:00:00
abstract::Modulation of the neuropeptide S (NPS) system has been linked to a variety of CNS disorders such as panic disorder, anxiety, sleeping disorders, asthma, obesity, PTSD, and substance abuse. In this study, a series of diphenyltetrahydro-1H-oxazolo[3,4-α]pyrazin-3(5H)-ones were synthesized and evaluated for antagonist ac...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn500113c
更新日期:2014-08-20 00:00:00
abstract::Post-translational modifications of proteins are ubiquitous in living organisms, as they enable an accurate control of the interactions of these macromolecules. For mechanistic studies, it would be highly advantageous to be able to produce in vitro post-translationally modified proteins with site-specificity. Here, we...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00761
更新日期:2021-01-19 00:00:00