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Hyung Gon Lee, Ji A Song, Dong Soo Han, Kyeong Wan Woo, Myung Ha Yoon
This study examined the effects of intrathecal areca nut on spinal nerve-ligated and chemotherapy-induced neuropathic pain (NP), and investigated the relevance of spinal 5-hydroxytryptamine (5-HT) and α2-adrenergic receptors to those effects. For drug administration, intrathecal catheters were inserted into the subarachnoid space of male Sprague-Dawley rats. NP was induced either by spinal nerve ligation (left spinal nerves L5 and L6) or by chemotherapeutic injection (intraperitoneal cisplatin, 2 mg/kg/day, once daily for 4 days)...
October 10, 2018: Pharmacology
Imane Frouni, Cynthia Kwan, Dominique Bédard, Sébastien Belliveau, Élodie Bourgeois-Cayer, Fleur Gaudette, Francis Beaudry, Adjia Hamadjida, Philippe Huot
L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective therapy for motor symptoms of Parkinson's disease (PD); however, with repeated administration, as many as 94% of PD patients develop complications such as L-DOPA-induced dyskinesia. We previously demonstrated that EMD-281,014, a highly selective serotonin 2A (5-HT2A ) receptor antagonist, reduces the severity of dyskinesia in the parkinsonian marmoset, without interfering with L-DOPA anti-parkinsonian benefit. Here, we assessed the effects of EMD-281,014 on L-DOPA-induced abnormal involuntary movements (AIMs) in the 6-hydroxydopamine (6-OHDA)-lesioned rat...
October 8, 2018: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
Xiaohu Wang, Nailong Cao, Jianshu Ni, Jiemin Si, Baojun Gu, Andersson Karl-Erik
OBJECTIVES: This study aimed to investigate the effects of ketanserin on micturition mediated via the 5-HT2A receptor in the motoneuron nucleus of the Lumbosacral cord, as reflected in high frequency oscillations (HFOs) of intravesical pressure and the external urethral sphincter electromyogram (EUS-EMG) in anesthetized male rats. METHODS:: Male Sprague-Dawley rats were used. Cystometry and EUS-EMG were performed in all rats under urethane anesthesia to examine the variations after successive intrathecal (i...
September 29, 2018: Neuroscience Letters
Amy J Eshleman, Katherine M Wolfrum, John F Reed, Sunyoung O Kim, Robert A Johnson, Aaron Janowsky
The use of new psychoactive substituted 2,5-dimethoxy-N-benzylphenethylamines is associated with abuse and toxicity in the United States and elsewhere and their pharmacology is not well known. This study compares the mechanisms of action of 2-(2,5-dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine (25D-NBOMe), 2-(4-ethyl-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25E-NBOMe), 2-(2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25H-NBOMe), 2-(((4-iodo-2,5-dimethoxyphenethyl)amino)methyl)phenol (25I-NBOH); and 2-(2,5-dimethoxy-4-nitrophenyl)-N-(2-methoxybenzyl)ethanamine) (25N-NBOMe) with hallucinogens and stimulants...
September 25, 2018: Biochemical Pharmacology
Ryan Patel, Anthony H Dickenson
Descending brainstem control of spinal nociceptive processing permits a dynamic and adaptive modulation of ascending sensory information. Chronic pain states are frequently associated with enhanced descending excitatory drive mediated predominantly through serotonergic neurones in the rostral ventromedial medulla. In this study, we examine the roles of spinal 5-HT2A and 5-HT3 receptors in modulating ascending sensory output in normal and neuropathic states. In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range neurones in the ventral posterolateral thalamus...
September 18, 2018: Neuropharmacology
Michelle Muñoz-Osses, Daniel Siegmund, Alejandra Gómez, Fernando Godoy, Angélica Fierro, Leonel Llanos, Daniel Aravena, Nils Metzler-Nolte
Cyrhetrenyl aldehyde derivatives [(η5-C5H4CHO)Re(CO)2PR3] with R = methyl (Me, 2a), phenyl (Ph, 2b), and cyclohexyl (Cy, 2c) were synthesized by a photochemical reaction from the starting material [(η5-C5H4CHO)Re(CO)3] (1) and the corresponding phosphines. The complexes were fully characterized by FT-IR, 1H, 13C and 31P NMR spectroscopy, elemental analysis and mass spectrometry. The molecular structures of 2a-c have also been determined. Electronic structure calculations by TD-DFT and electrochemical studies are in sound agreement with the effect of the substitution of one carbonyl group by a phosphine ligand...
September 18, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Kelsey S Hideshima, Ashkhan Hojati, Justin M Saunders, Doan M On, Mario de la Fuente Revenga, Jong M Shin, Ana Sánchez-González, Cassandra M Dunn, Alexander B Pais, Anthony C Pais, Michael F Miles, Jennifer T Wolstenholme, Javier González-Maeso
BACKGROUND: Serotonin 5-HT2A and metabotropic glutamate 2 (mGlu2) are neurotransmitter G protein-coupled receptors (GPCRs) involved in the signaling mechanisms underlying psychosis and schizophrenia treatment. Previous findings in mGlu2 knockout (KO) mice suggested that mGlu2 is necessary for head-twitch behavior, a rodent phenotype characteristic of hallucinogenic 5-HT2A receptor agonists. However, the role of mGlu2 in the behavioral effects induced by antipsychotic drugs remains poorly understood...
September 12, 2018: Psychopharmacology
Zakariya Nawasreh, Gabrielle Adams, Olivia Pryzbylkowski, David Logerstedt
Background: There are inconsistencies in the reported rates of second anterior cruciate ligament (ACL) injuries per limb, patients' sex and graft types after primary ACL reconstruction (ACLR). There are also inconsistencies regarding the influence of these factors on the occurrence of second ACL injury after primary ACLR. Purpose: To determine the rate of second ACL injury, to either the ipsilateral graft or contralateral healthy ACL, as influenced by sex, age, and graft types and to determine the influence of sex, age, and graft types on the occurrence of second ACL injury after primary ACLR...
August 2018: International Journal of Sports Physical Therapy
Y C Luo, Y Q Zhang, K Hu, Z Zhang, M Q Xiong, W H Hu, M L Dong, M Shang
Objective: To explore the role of 5-HT(2A)R/PKC pathway in mediating long-term facilitation (LTF) of carotid sinus nerve (CSN) discharge in chronic intermittent hypoxia (CIH) rats. Methods: With number table, 24 adult SD rats were randomly divided into saline control group (group A, n =6), 5-HT(2A)R antagonist (ketanserin) group (group B, n =6), PKC inhibitor (PKC θ-pseudosubstrate) group (group C, n =6) and combined ketanserin with PKC θ-pseudosubstrate group (group D, n =6). All rats were placed into the animal chambers for CIH treatment, 8 h per day (from 9: 00 to 17: 00) for 4 consecutive weeks...
August 12, 2018: Chinese Journal of Tuberculosis and Respiratory Diseases
Daniel Avesar, Emily K Stephens, Allan T Gulledge
Neuromodulatory transmitters, such as serotonin (5-HT), selectively regulate the excitability of subpopulations of cortical projection neurons to gate cortical output to specific target regions. For instance, in the mouse prelimbic cortex, 5-HT selectively excites commissurally projecting (COM) intratelencephalic neurons via activation of 5-HT2A (2A) receptors, while simultaneously inhibiting, via 5-HT1A (1A) receptors, corticofugally projecting pyramidal neurons targeting the pons. Here we characterize the physiology, morphology, and serotonergic regulation of corticoamygdalar (CAm) projection neurons in the mouse prelimbic cortex...
2018: Frontiers in Neural Circuits
Faezeh Taghavi, Mostafa Gholizadeh, Amir Sh Saljooghi, Mohammad Ramezani
Cu(ii) immobilized on deferasirox loaded amine functionalized magnetic nanoparticles (Cu(ii)/Fe3 O4 @APTMS-DFX) as a novel magnetically recyclable heterogeneous catalyst is able to catalyze the [3 + 2] cycloaddition reactions of various organic nitriles with sodium azide. Using this method, a series of 5-substituted-1 H -tetrazoles under mild conditions in DMSO were prepared. The reaction involves mild reaction conditions with efficient transformation capability. The developed catalyst could be easily separated by applying an external magnetic field...
October 1, 2017: MedChemComm
Thomas W Flanagan, Charles D Nichols
Serotonin (5-hydroxytryptamine, 5-HT)2A receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the medical community and populace at large. One emerging therapeutic area that holds significant promise is their use as anti-inflammatory agents...
August 13, 2018: International Review of Psychiatry
Yong Zhang, Yupu Liang, Matthew Randesi, Vadim Yuferov, Connie Zhao, Mary Jeanne Kreek
Prescription opioid abuse, for example of oxycodone, is a pressing public health issue. This study focuses on how chronic oxycodone self-administration (SA) affects the reward pathways in the mouse brain. In this study, we tested the hypothesis that the expression of reward-related genes in the ventral and dorsal striatum, areas involved in different aspects of opioid addiction models, was altered within 1 h after chronic oxycodone SA, using transcriptome-wide sequencing (RNA-seq). Based on results from earlier human genetic and rodent preclinical studies, we focused on a set of genes that may be associated with the development of addictive diseases and the rewarding effect of drugs of abuse, primarily in the opioid, stress response and classical neurotransmitter systems...
July 29, 2018: Neuroscience
Ditte Marie Jensen, Gry Freja Skovsted, Jens Lykkesfeldt, Rasmus Dreier, Jais Oliver Berg, Jørgen Lykke Jeppesen, Majid Sheykhzade, Steffen Loft, Peter Møller
Animal studies have shown that titanium dioxide (TiO2 ) exposure affects arterial vasomotor function, whereas little is known about the effects in arteries from humans. This study investigated vasomotor responses after direct exposure of human subcutaneous arteries to food-grade TiO2 (E171) (14 or 140 μg/ml) for 30 min and 18 h. Vasomotor responses to bradykinin, 5-hydroxytryptamine (5-HT), sarafotoxin 6c (S6c) and nitroglycerin were recorded in wire-myographs. Vasoconstrictor responses to 5-HT were increased in arteries exposed to E171 for 18 h (P < 0...
July 7, 2018: Food and Chemical Toxicology
M Y Liu, L J Zhang
Objective: Exploring the modulation of periphery and central serotonin (5-hydroxytrytamine, 5-HT) and 5-HT(2A) receptor (5-HT(2A)R) in mice with heart failure during the process of heart failure and after treatment. Methods: Thirty mice were allocated into three groups randomly including normal group (NG), heart failure group (HFG) and treatment group (TG) ( n =10). Mice in the NG were sacrificed after evaluating left ventricular ejection fraction (EF) with echocardiogram. Mice in HFG and TG experienced myocardial infarction surgery to achieve EF≤30%, HFG was treated with saline and TG with Ginkgo biloba pills (GBP), once a day for 4 weeks, then EF was assessed again before sacrifice...
July 3, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Adjia Hamadjida, Stephen G Nuara, Dominique Bédard, Fleur Gaudette, Francis Beaudry, Jim C Gourdon, Philippe Huot
Blockade of serotonin 2A (5-HT2A ) receptors is regarded as an anti-dyskinetic and anti-psychotic strategy in Parkinson's disease (PD). However, the 5-HT2A antagonists tested so far exhibited affinity for other receptors, which might have played a role in their action. EMD-281,014 is the most selective 5-HT2A antagonist available, with approximately 2,000-fold selectivity over serotonin 2C (5-HT2C ) receptors. EMD-281,014 was previously tested in the clinic and has high translational potential. In the present study, we assessed the effect of EMD-281,014 on dyskinesia and psychosis in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmoset...
September 1, 2018: Neuropharmacology
Iris E C Sommer, Hidde Kleijer, Lucy Visser, Teus van Laar
Hallucinations, visual, auditory or in another sensory modality, often respond well to treatment in patients with schizophrenia. Some, however, do not and can be very chronic and debilitating. We present a patient with schizophrenia with intractable hallucinations despite state of the art care, including high-dose clozapine and transcranial magnetic stimulation. Based on the possible role of the 5-HT2A receptor in hallucinations, we treated her with the antihypertensive drug ketanserin, a 5-HT2A receptor antagonist...
June 27, 2018: BMJ Case Reports
Lina Nie, Tianqi Di, Yu Li, Peng Cheng, Ming Li, Jun Gao
Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D2 receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT2A receptors on dopamine D2 -mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test...
August 2018: Pharmacology, Biochemistry, and Behavior
Samy Murat, Mathilde Bigot, Jonathan Chapron, Gabriele M König, Evi Kostenis, Giuseppe Battaglia, Ferdinando Nicoletti, Emmanuel Bourinet, Joël Bockaert, Philippe Marin, Franck Vandermoere
The serotonin 5-HT2A and glutamate mGlu2 receptors continue to attract particular attention, given their implication in psychosis associated with schizophrenia and the mechanism of action of atypical antipsychotics and a new class of antipsychotics, respectively. A large body of evidence indicates a functional crosstalk between both receptors in the brain, but the underlying mechanisms are not entirely elucidated. Here, we have explored the influence of 5-HT2A receptor upon the phosphorylation pattern of mGlu2 receptor in light of the importance of specific phosphorylation events in regulating G protein-coupled receptor signaling and physiological outcomes...
June 1, 2018: Molecular Psychiatry
Crystal Li, Juliana Silva, Ezgi Ozturk, Gabriella Dezsi, Terence J O'Brien, Thibault Renoir, Nigel C Jones
Patients with epilepsy often have mood disorders, and these are commonly treated with antidepressant drugs. Although these drugs are often successful in mitigating depressive symptoms, how they affect the epileptogenic processes has been little studied. Recent evidence has demonstrated that treatment with selective serotonin reuptake inhibitor (SSRI) antidepressant drugs adversely promotes epileptogenesis, which may be of great concern considering the number of patients exposed to these drugs. This study investigated 5-HT2A receptor signaling as a potential mechanism driving the pro-epileptogenic effects of the prototypical SSRI fluoxetine...
July 2018: Epilepsia
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