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Manoela V Fogaça, Alline C de Campos, Ludmila D Coelho, Ronald S Duman, Francisco S Guimarães
Repeated injections of cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, attenuate the anxiogenic effects induced by Chronic Unpredictable Stress (CUS). The specific mechanisms remain to be fully understood but seem to involve adult hippocampal neurogenesis and recruitment of endocannabinoids. Here we investigated for the first time if the behavioral and pro-neurogenic effects of CBD administered concomitant the CUS procedure (14 days) are mediated by CB1 , CB2 or 5HT1A receptors, as well as CBD effects on dendritic remodeling and on intracellular/synaptic signaling (fatty acid amide hydrolase - FAAH, Akt, GSK3β and the synaptic proteins Synapsin Ia/b, mGluR1 and PSD95)...
March 3, 2018: Neuropharmacology
Yueh-Ming Tai, Chih-Yuan Ko, Chen-Cheng Lin, Yu-Yue Wan, Jing-Yi Chung, Yia-Ping Liu
OBJECTIVE: Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT...
February 2018: Psychiatry Investigation
Nicola Maggio, Efrat Shavit Stein, Menahem Segal
Epilepsy is a devastating disease, with cognitive and emotional consequences that are not curable. In recent years, it became apparent that cannabinoids help patients to cope with epilepsy. We have studied the effects of cannabidiol (CBD) on the ability to produce long term potentiation (LTP) in stratum radiatum of CA1 region of the mouse hippocampus. Exposure to seizure-producing pilocarpine reduced the ability to generate LTP in the slice. Pre-exposure to CBD prevented this effect of pilocarpine. Furthermore, CBD caused a marked increase in ability to generate LTP, an effect that was blocked by calcium store antagonists as well as by a reduction in serotonin tone...
2018: Frontiers in Molecular Neuroscience
Ya Fatou Njie-Mbye, Jenaye Robinson, Leah Mitchell-Bush, Marshalyn Mckoy, Catherine A Opere, Sunny E Ohia, Naj Sharif
PURPOSE: To determine the serotonergic (5HT) receptor subtype mediating the contraction of bovine posterior ciliary arteries (BPCAs) in vitro. METHODS: Longitudinal isometric tension was measured in BPCA strips (4-5 mm) mounted in 25 mL organ baths containing oxygenated Krebs solution at 37°C. Cumulative contractile concentration-response (C-R) curves were generated for various 5-HT agonists to assess their potencies and maximal degrees of contraction. Multiple agonist C-R curves were also constructed in the presence and absence of receptor-selective antagonists to determine antagonist potencies using Schild plots...
January 25, 2018: Journal of Ocular Pharmacology and Therapeutics
William Pote, Shamiso Musarira, Donald Chuma, Louis L Gadaga, Ellen Mwandiringana, Dexter Tagwireyi
ETHNOPHARMACOLOGICAL RELEVANCE: Boophone disticha is one of the most important medicinal bulbs of Southern Africa. Previous in vitro studies have shown that it's crude ethanolic extracts and some alkaloidal phytoconstituents possesses high affinity for the serotonin transporter protein (SERT) and serotonin receptor 1a (5HT1a ) which are both implicated in the pathogenesis and treatment of anxiety disorders. However, there are no in vivo studies that validates the anxiolytic actions of the plant...
March 25, 2018: Journal of Ethnopharmacology
Megala Narasingam, Kamini Vijeepallam, Zahurin Mohamed, Vijayapandi Pandy
This study presents anxiolytic- and antidepressant-like effects of a methanolic extract of Morinda citrifolia Linn. (noni) fruit (MMC) in well-established mouse models of anxiety and depression. The administration of MMC (1 g/kg, p.o.) and diazepam (1 mg/kg, i.p.) significantly attenuated anxiety-like behaviour in mice by increasing the percentage of time spent and number of entries in the open arms in the elevated plus maze (EPM), and significantly enhanced the exploration in the light box in the light/dark test (LDT)...
December 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Wei-Hsi Chen, Yuan-Hsiang Chu, Kuo-Yen Chen
OBJECTIVES: Spontaneous orgasm is characterized by a spontaneous onset of orgasm without any preceding sexual or nonsexual trigger. It sheds insight on the mechanisms underlying orgasms and the sexual response cycle in humans. METHODS: We report a male patient of repetitive spontaneous orgasm under trazodone treatment and systematically review the literature on drug-associated spontaneous orgasm (DASO). RESULTS: A total of 25 patients (18 women and 7 men), including our reported case, experienced 27 DASO events...
January 2018: Clinical Neuropharmacology
Mariana G Fronza, Lucimar M Pinto Brod, Angela Maria Casaril, Manoela Sacramento, Diego Alves, Lucielli Savegnago
A series of phenylselanyl-1H-1,2,3-triazole-4-carbonitriles with different substituents were screened for their binding affinity with serotonin transporter (SERT) and dopamine transporter (DAT) by docking molecular. 5-(4methoxyphenyl)-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazole-4-carbonitrile (SeTACN) exhibited the best conformation with SERT even higher than fluoxetine and serotonin, suggesting a competitive inhibition. SeTACN demonstrated additional affinity to other serotonergic receptors involved in antidepressant effects: 5HT1a, 5HT2a and 5HT3...
2017: PloS One
Franklin R Schneier, Danielle M Moskow, Tse-Hwei Choo, Hanga Galfalvy, Raphael Campeas, Arturo Sanchez-Lacay
BACKGROUND: Separation anxiety disorder was recently recognized by fifth edition of the Diagnostic and Statistical Manual of Mental Disorders as a diagnosis in adults, but no publications to date have characterized a sample of patients seeking treatment for adult separation anxiety disorder (ASAD) or assessed treatment efficacy. We hypothesized that vilazodone, a selective serotonin reuptake inhibitor (SSRI) and serotonin 1a (5HT1a ) receptor partial agonist, would have efficacy in ASAD, because SSRIs have appeared efficacious in children with mixed diagnoses including separation anxiety disorder and in animal models of separation anxiety...
December 2017: Depression and Anxiety
Yongjun Qian, Yue Cao, Bowen Deng, Guang Yang, Jiayun Li, Rui Xu, Dandan Zhang, Juan Huang, Yi Rao
Our understanding of the molecular mechanisms underlying sleep homeostasis is limited. We have taken a systematic approach to study neural signaling by the transmitter 5-hydroxytryptamine (5-HT) in drosophila. We have generated knockout and knockin lines for Trh, the 5-HT synthesizing enzyme and all five 5-HT receptors, making it possible for us to determine their expression patterns and to investigate their functional roles. Loss of the Trh, 5HT1a or 5HT2b gene decreased sleep time whereas loss of the Trh or 5HT2b gene diminished sleep rebound after sleep deprivation...
October 6, 2017: ELife
Mingjun Xiang, Yuting Jiang, Zhiying Hu, Yang Yang, Benson O A Botchway, Marong Fang
BACKGROUND/AIMS: Serotonin 5HT2A and 5HT1A receptors (5HT2AR, 5HT1AR) have the closest connection to anxiety-like behavior in post-traumatic stress disorder (PTSD). However, the underlying mechanism remains unclear. In this study, we explored the connection between 5HT2A and 5HT1A receptors and anxiety-like behavior. METHODS: In the PTSD animal model, mice were exposed to conditioned fear stress coupled with single-prolonged stress (CF+SPS). Post stress infliction and behavioral tests, of which include open field, freezing behavior and elevated plus maze tests were carried out to examine establishment of the proposed model...
October 6, 2017: Neuro-Signals
Madeline C Pelz, Kathleen D Schoolcraft, Chloe Larson, Mitchell G Spring, Hassan H López
Cannabidiol (CBD) is a phytocannabinoid that has demonstrated anticonvulsant efficacy in several animal models of seizure. The current experiment validated CBD's anticonvulsant effect using the acute pentylenetetrazol (PTZ) model. Furthermore, it tested whether CBD reduces seizure activity by interacting with either the serotonergic 5HT1A or 5HT2A receptor. 120 male adolescent Wistar-Kyoto rats were randomly assigned to 8 treatment groups in two consecutive experiments. In both experiments, subjects received either CBD (100mg/kg) or vehicle 60min prior to seizure testing...
June 15, 2017: Epilepsy & Behavior: E&B
C William Heise, Hannah Malashock, Daniel E Brooks
BACKGROUND: Vilazodone is an antidepressant with selective serotonin reuptake inhibition and partial 5HT1A agonism. Serotonin syndrome is believed to be due to excessive stimulation of 5-HT2A and 5-HT1A receptors, resulting in the clinical triad of altered mentation, autonomic instability and neuromuscular abnormalities. The goal of this study is to define serotonergic effects after vilazodone exposure. METHODS: A retrospective review of two databases: the American Association of Poison Controls Centers' National Poison Data System (NPDS) and the American College of Medical Toxicology's Toxicology Investigators Consortium (ToxIC Registry)...
November 2017: Clinical Toxicology
Peter J McLaughlin, Julia E Jagielo-Miller, Emily S Plyler, Kerry K Schutte, V Kiran Vemuri, Alexandros Makriyannis
RATIONALE: Cannabinoid CB1 inverse agonists hold therapeutic promise as appetite suppressants but have produced suicidal behaviors among a small subpopulation in clinical trials. Anatomical and pharmacological evidence implicate the 5HT1A serotonin receptor in suicide in humans and impulsivity in humans and animals. OBJECTIVE: The objective of the study is to assess whether 5HT1A blockade is necessary for CB1 ligands to produce impulsivity. METHODS: Sprague Dawley rats were administered the CB1 inverse agonist AM 251, the CB1 antagonist AM 6527, or the peripherally restricted antagonist AM 6545, with or without pretreatment with the 5HT1A antagonist WAY 100,635 (WAY) on the paced fixed consecutive number (FCN) task, which measures choice to terminate a chain of responses prematurely...
March 2017: Psychopharmacology
Sudarat Nimitvilai, Marcelo F Lopez, Patrick J Mulholland, John J Woodward
Alcohol abuse disorders are associated with dysfunction of frontal cortical areas including the orbitofrontal cortex (OFC). The OFC is extensively innervated by monoamines, and drugs that target monoamine receptors have been used to treat a number of neuropsychiatric diseases, including alcoholism. However, little is known regarding how monoamines affect OFC neuron excitability or whether this modulation is altered by chronic exposure to ethanol. In this study, we examined the effect of dopamine, norepinephrine, and serotonin on lOFC neuronal excitability in naive mice and in those exposed to chronic intermittent ethanol (CIE) treatment...
August 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Sara Guariento, Silvia Franchini, Michele Tonelli, Paola Fossa, Claudia Sorbi, Elena Cichero, Livio Brasili
The 5-hydroxytryptamine (5-HT1A) receptors represent an attractive target in drug discovery. In particular, 5-HT1A agonists and partial agonists are deeply investigated for their potential role in the treatment of anxiety, depression, ischaemic brain disorder and more recently, of pain. On the other hand, 5-HT1A antagonists have been revealed promising compounds in cognition disorders and, lately, in cancer. Thus, the discovery of 5HT1A ligands is nowadays an appealing research activity in medicinal chemistry...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
Azhdar Heydari, Shima Davoudi
PURPOSE: Serotonin is a key regulatory neurotransmitter in the CNS which plays an important role in seizure through different receptors, especially the 5HT1A subtype. The role of sertraline through the 5HT1A receptor and nitric oxide interaction on the PTZ-induced seizure threshold was investigated in this study. METHOD: In this study, 70 white male mice were randomly divided into 10 groups including intact control, sham-control and eight experimental groups which received sertraline, 8-OH-DPAT, WAY100635, WAY100635+sertraline, WAY100635+8-OH-DPAT, L-NAME, L-NAME+sertraline and L-NAME+8-OH-DPAT...
February 2017: Seizure: the Journal of the British Epilepsy Association
Jessica M D'Amico, Annie A Butler, Martin E Héroux, Florence Cotel, Jean-François M Perrier, Jane E Butler, Simon C Gandevia, Janet L Taylor
KEY POINTS: In the adult turtle spinal cord, action potential generation in motoneurones is inhibited by spillover of serotonin to extrasynaptic serotonin 1A (5-HT1A ) receptors at the axon initial segment. We explored whether ingestion of the 5-HT1A receptor partial agonist, buspirone, decreases motoneurone excitability in humans. Following ingestion of buspirone, two tests of motoneurone excitability showed decreases. F-wave areas and persistence in an intrinsic muscle of the hand were reduced, as was the area of cervicomedullary motor evoked potentials in biceps brachii...
March 1, 2017: Journal of Physiology
Srikanta Chowdhury, Akihiro Yamanaka
Orexin/hypocretin neurons play a crucial role in the regulation of sleep/wakefulness, primarily in the maintenance of wakefulness. These neurons innervate wide areas of the brain and receive diverse synaptic inputs including those from serotonergic (5-HT) neurons in the raphe nucleus. Previously we showed that pharmacological application of 5-HT directly inhibited orexin neurons via 5-HT1A receptors. However, it was still unclear how 5-HT neurons regulated orexin neurons since 5-HT neurons contain not only 5-HT but also other neurotransmitters...
November 8, 2016: Scientific Reports
John L Beyer, Richard H Weisler
The lifetime prevalence of major depressive episodes in the United States is nearly 17%. Clinical trials and clinical effectiveness studies have demonstrated that many patients will fail to achieve remission using traditional monotherapy, contributing to significant morbidity and suffering. Because of this, augmentation strategies have been proposed to improve both treatment response and remission. Areas covered: Brexpiprazole is a second generation antipsychotic (SGA) approved by the US FDA in 2015 as an add-on treatment to an antidepressant medication for the treatment of adults with MDD, based on the results of two large-scale, randomized, placebo-controlled trials...
December 2016: Expert Opinion on Pharmacotherapy
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