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https://www.readbyqxmd.com/read/29452148/complete-inhibition-of-fetal-movement-in-the-day-40-pregnant-goat-model-by-the-piperidine-alkaloid-anabasine-but-not-related-alkaloids
#1
B T Green, S T Lee, J W Keele, K D Welch, D Cook, J A Pfister, W R Kem
Four chemically similar alkaloids, anabasine, anabaseine, epibatidine and dimethylphenylpiperazinium (DMPP), are potent nicotinic acetylcholine receptor agonists of fetal muscle nicotinic acetylcholine receptors in human TE-671 cells. Based on results with these cells, we hypothesized that the alkaloids would completely inhibit ultrasound-monitored fetal movement in a goat model. Different, single doses of anabasine, anabaseine, epibatidine, DMPP, or saline control were administered I.V. to pregnant goats on day 40 of gestation and the number of fetal movements per 5 min sample was measured by ultrasound at times 0, 0...
February 13, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29451400/designing-selective-modulators-for-the-nicotinic-receptor-subtypes-challenges-and-opportunities
#2
Dina Manetti, Cristina Bellucci, Niccolò Chiaramonte, Silvia Dei, Elisabetta Teodori, Maria Novella Romanelli
Nicotinic receptors are membrane proteins involved in several physiological processes. They are considered suitable drug targets for various CNS disorders or conditions, as shown by the large number of compounds which have entered clinical trials. In recent years, nonconventional agonists have been discovered: positive allosteric modulators, allosteric agonists, site-specific agonists and silent desensitizers are compounds able to modulate the receptor interacting at sites different from the orthodox one, or to desensitize the receptor without prior opening...
February 16, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29449430/a-critical-role-for-the-nucleus-reuniens-in-long-term-but-not-short-term-associative-recognition-memory-formation
#3
G R I Barker, E C Warburton
Recognition memory for single items requires the perirhinal cortex (PRH), while recognition of an item and its associated location, requires a functional interaction between the PRH, hippocampus (HPC) and medial prefrontal cortex (mPFC). While the precise mechanisms through which these interactions are effected are unknown, the nucleus reuniens (NRe) has bidirectional connections with each regions and hence may play a role in recognition memory. Here we investigated, in male rats, whether specific manipulations of NRe function affected performance of recognition memory for single items, object location or object-in-place associations...
February 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29444518/effects-of-environmental-enrichment-on-nicotine-sensitization-in-rats-neonatally-treated-with-quinpirole-analyses-of-glial-cell-line-derived-neurotrophic-factor-and-implications-towards-schizophrenia
#4
Russell W Brown, Marjorie A Schlitt, Alex S Owens, Caitlynn C DePreter, Elizabeth D Cummins, Seth L Kirby, W Drew Gill, Katherine C Burgess
The current study analyzed the effects of environmental enrichment versus isolation housing on the behavioral sensitization to nicotine in the neonatal quinpirole (NQ; dopamine D2-like agonist) model of dopamine D2 receptor supersensitivity, a rodent model of schizophrenia. NQ treatment in rats increases dopamine D2 receptor sensitivity throughout the animal's lifetime, consistent with schizophrenia. Animals were administered NQ (1 mg/kg) or saline (NS) from postnatal day (P)1 to P21, weaned, and immediately placed into enriched housing or isolated in wire cages throughout the experiment...
February 14, 2018: Developmental Neuroscience
https://www.readbyqxmd.com/read/29438564/erratum-for-%C3%AE-7-nicotinic-acetylcholine-receptor-agonist-ameliorates-nicotine-plus-high-fat-diet-induced-hepatic-steatosis-in-male-mice-by-inhibiting-oxidative-stress-and-stimulating-ampk-signaling
#5
https://www.readbyqxmd.com/read/29435707/antinociceptive-effects-of-novel-epibatidine-analogs-through-activation-of-%C3%AE-4%C3%AE-2-nicotinic-receptors
#6
Weiwei Li, Jingyi Cai, Benjamin H Wang, Lanting Huang, Jing Fan, Yun Wang
The study of α4β2 nicotinic receptors has provided new indications in the treatment of pain. Efforts have been made to explore new α4β2 nicotinic receptor agonists, including TC-2559, as antinociceptive drugs. In this study, we discovered a set of novel epibatidine analogs with strong binding affinities to the α4β2 nicotinic receptors. Among these compounds, C-159, C-163, and C-9515 attenuated formalin-induced nociceptive responses in mice; C-9515 caused the most potent analgesic effect, which was blocked by mecamylamine, a non-selective nicotinic receptor antagonist...
February 2, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29429366/the-enhancement-of-serotonin-induced-contraction-of-rat-femoral-artery-is-mediated-by-angiotensin-ii-release-from-intact-endothelium
#7
Marko Stojanović, Milica Prostran, Miroslav Radenković
We have performed an in vitro study on isolated intact or denuded femoral artery (FA) of healthy, diabetic, and/or rats submitted to the FA occlusion. The aim was to determine the contribution of endothelium and endothelial dysfunction (ED) on serotonin-induced action in FA. Further, the contribution of angiotensin II and cyclooxygenase products of arachidonic acid was investigated. A marker of ED, vWF was measured in animal serum. Serotonin induced contraction-dependent contraction of isolated FA, which was increased in preparations with endothelium...
February 10, 2018: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29428175/beyond-the-channel-metabotropic-signaling-by-nicotinic-receptors
#8
REVIEW
Nadine Kabbani, Robert A Nichols
The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel (LGIC) that plays an important role in cellular calcium signaling and contributes to several neurological diseases. Agonist binding to the α7 nAChR induces fast channel activation followed by inactivation and prolonged desensitization while triggering long-lasting calcium signaling. These activities foster neurotransmitter release, synaptic plasticity, and somatodendritic regulation in the brain. We discuss here the ability of α7 nAChRs to operate in ionotropic (α7 i ) and metabotropic (α7 m ) modes, leading to calcium-induced calcium release (CICR) and G protein-associated inositol trisphosphate (IP 3 )-induced calcium release (IICR), respectively...
February 7, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29427655/nicotinic-acetylcholine-receptors-are-associated-with-ketamine-induced-neuronal-apoptosis-in-the-developing-rat-retina
#9
Lingqi Gao, Junde Han, Jie Bai, Jing Dong, Sen Zhang, Mazhong Zhang, Jijian Zheng
Early synchronized spontaneous network activity is a hallmark of the brain growth spurt period, during which general anesthetics cause widespread neuronal apoptosis and subsequent cognitive dysfunction. However, the relationship of such activity to anesthetic-induced neuronal apoptosis remains to be determined. In this study, we utilized patch-clamp electrophysiological recording, immunohistochemistry, and TUNEL assays to investigate the potential roles of spontaneous network activity in ketamine-induced neuronal apoptosis during early development...
February 7, 2018: Neuroscience
https://www.readbyqxmd.com/read/29427069/new-scaffold-for-lead-compounds-to-treat-methamphetamine-use-disorders
#10
Na-Ra Lee, Guangrong Zheng, Peter A Crooks, Michael T Bardo, Linda P Dwoskin
Despite increased methamphetamine use worldwide, pharmacotherapies are not available to treat methamphetamine use disorder. The vesicular monoamine transporter-2 (VMAT2) is an important pharmacological target for discovery of treatments for methamphetamine use disorder. VMAT2 inhibition by the natural product, lobeline, reduced methamphetamine-evoked dopamine release, methamphetamine-induced hyperlocomotion, and methamphetamine self-administration in rats. Compared to lobeline, lobelane exhibited improved affinity and selectivity for VMAT2 over nicotinic acetylcholine receptors...
February 9, 2018: AAPS Journal
https://www.readbyqxmd.com/read/29426250/%C3%AE-conotoxin-imi-modified-polymeric-micelles-as-potential-nanocarriers-for-targeted-docetaxel-delivery-to-%C3%AE-7-nachr-overexpressed-non-small-cell-lung-cancer
#11
Dong Mei, Libo Zhao, Binlong Chen, Xiaoyan Zhang, Xiaoling Wang, Zhiying Yu, Xin Ni, Qiang Zhang
A micelle system modified with α-Conotoxin ImI (ImI), a potently antagonist for alpha7 nicotinic acetylcholine receptor (α7-nAChR) previously utilized for targeting breast cancer, was constructed. Its targeting efficiency and cytotoxicity against non-small cell lung cancer (NSCLC) highly expressing α7-nAChR was investigated. A549, a non-small cell lung cancer cell line, was selected as the cell model. The cellular uptake study showed that the optimal modification ratio of ImI on micelle surface was 5% and ImI-modification increased intracellular delivery efficiency to A549 cells via receptor-mediated endocytosis...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29423839/molecular-neuronal-and-behavioral-effects-of-ethanol-and-nicotine-interactions
#12
Paul M Klenowski, Andrew R Tapper
Ethanol and nicotine can modulate the activity of several neurotransmitter systems and signalling pathways. Interactions between ethanol and nicotine can also occur via common molecular targets including nicotinic acetylcholine receptors (nAChRs). These effects can induce molecular and synaptic adaptations that over time, are consolidated in brain circuits that reinforce drug-seeking behavior, contribute to the development of withdrawal symptoms during abstinence and increase the susceptibility to relapse. This chapter will discuss the acute and chronic effects of ethanol and nicotine within the mesolimbic reward pathway and brain circuits involved in learning, memory, and withdrawal...
February 9, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29423392/neurochemical-alterations-in-sudden-unexplained-perinatal-deaths-a-review
#13
REVIEW
Nazeer Muhammad, Muhammad Sharif, Javeria Amin, Riffat Mehboob, Syed Amir Gilani, Nargis Bibi, Hasnain Javed, Naseer Ahmed
Sudden unexpected perinatal collapse is a major trauma for the parents of victims. Sudden infant death syndrome (SIDS) is unexpected and mysterious death of an apparently healthy neonate from birth till 1 year of age without any known causes, even after thorough postmortem investigations. However, the incidence of sudden intrauterine unexplained death syndrome (SIUDS) is seven times higher as compared with SIDS. This observation is approximated 40-80%. Stillbirth is defined as death of a fetus after 20th week of gestation or just before delivery at full term without a known reason...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29420933/precisely-timed-nicotinic-activation-drives-sst-inhibition-in-neocortical-circuits
#14
Joanna Urban-Ciecko, Jean-Sebastien Jouhanneau, Stephanie E Myal, James F A Poulet, Alison L Barth
Sleep, waking, locomotion, and attention are associated with cell-type-specific changes in neocortical activity. The effect of brain state on circuit output requires understanding of how neuromodulators influence specific neuronal classes and their synapses, with normal patterns of neuromodulator release from endogenous sources. We investigated the state-dependent modulation of a ubiquitous feedforward inhibitory motif in mouse sensory cortex, local pyramidal (Pyr) inputs onto somatostatin (SST)-expressing interneurons...
February 7, 2018: Neuron
https://www.readbyqxmd.com/read/29413432/effects-of-nicotine-containing-and-nicotine-free-e-cigarette-refill-liquids-on-intracranial-self-stimulation-in-rats
#15
Andrew C Harris, Peter Muelken, John R Smethells, Katrina Yershova, Irina Stepanov, Thao Tran Olson, Kenneth J Kellar, Mark G LeSage
BACKGROUND: Animal models are needed to inform FDA regulation of electronic cigarettes (ECs) because they avoid limitations associated with human studies. We previously reported that an EC refill liquid produced less aversive/anhedonic effects at a high nicotine dose than nicotine alone as measured by elevations in intracranial self-stimulation (ICSS) thresholds, which may reflect the presence of behaviorally active non-nicotine constituents (e.g., propylene glycol) in the EC liquids...
February 1, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29411706/-maternal-bonding-style-cholinergic-receptor-gene-polymorphisms-in-association-with-smoking-related-depressive-symptoms
#16
Iren Csala, Peter Dome, Judit Lazary
Backgorund: There is accumulating evidence on the association between the cholinergic system and nicotine dependence (ND) in the literature and the bidirectional relationship of ND and depression. However, the molecular background of the development of ND and related affective phenotype is not clear. METHODS: We recruited 255 tretament-seeking smokers into our study. For phenotyping assessments we used the Fagerstrom Nicotine Dependence Test; The Minnessotta Nicotine Withdrawal Scale; the Zung Self-Rating Depression Scale and the Parental Bonding Instrument...
December 2017: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/29407477/mutually-augmenting-interactions-of-dextromethorphan-and-sazetidine-a-for-reducing-nicotine-self-administration-in-rats
#17
Edward D Levin, Corrine Wells Susan Slade, Amir H Rezvani
A variety of nicotinic drug treatments have been found to decrease nicotine self-administration. However, interactions of drugs affecting different nicotinic receptor subtypes have not been much investigated. This study investigated the interactions between dextromethorphan, which blocks nicotinic α3β2 receptors as well as a variety of other receptors with sazetidine-A which is a potent and selective α4β2 nicotinic receptor partial agonist with desensitizing properties. This interaction was compared with dextromethorphan combination treatment with mecamylamine, which is a nonspecific nicotinic channel blocker...
January 30, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29406991/a-new-etiologic-model-for-alzheimers-disease
#18
Kathryn A Schiel
This etiologic model proposes that Alzheimers Disease (AD) arises when an unusually rapid increase in ventricle volume triggers axon stretch that culminates in the physical separation of trans-synaptic proteins. As a result, these proteins, such as neurexin, neuroligin, N-Cadherin and Amyloid Precursor Protein (APP), experience a change in the configuration of their cytoplasmic tail, so that instead of transmitting signals to create and maintain synaptic structure they activate enzymes, and generate molecules, that stimulate neurite growth; for example, the transformation of the N-Cadherin tail dissolves its complex with presenilin and β-catenin triggering activation of glycogen synthase kinase 3 beta (GSK3β) and cytoskeletal disruption...
February 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29405928/structural-identification-of-the-nicotinic-receptor-ion-channel
#19
Jean-Pierre Changeux
The structural identification of the cationic channel of the acetylcholine nicotinic receptor involved its biochemical tagging by channel blockers, followed by site-directed mutagenesis analyses reported in two papers in 1988. The ion channel was demonstrated to be lined by the transmembrane segment MII, in which the binding sites of channel blockers are "framed" by anionic rings.
February 2018: Trends in Neurosciences
https://www.readbyqxmd.com/read/29405451/nicotinic-activity-layer-specifically-modulates-synaptic-potentiation-in-the-mouse-insular-cortex
#20
Hiroki Toyoda
Nicotinic acetylcholine receptors (nAChRs) in the insular cortex play an important role in nicotine addiction, but its cellular and synaptic mechanisms underlying nicotine addiction still remain unresolved. In layer 5 pyramidal neurons of the mouse insular cortex, activation of nAChRs suppresses synaptic potentiation through enhancing GABAergic synaptic transmission via activation of β2-containing nAChRs in non-fast-spiking (non-FS) interneurons. However, it has not been addressed whether and how activation of nAChRs modulates synaptic plasticity in layer 3 and 6 pyramidal neurons of the insular cortex...
February 6, 2018: European Journal of Neuroscience
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